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Seminars in Immunopathology
Published in: Seminars in Immunopathology 6/2012

01-11-2012 | Review

Immune response and immunopathology during toxoplasmosis

Authors: Christopher D. Dupont, David A. Christian, Christopher A. Hunter

Published in: Seminars in Immunopathology | Issue 6/2012

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Abstract

Toxoplasma gondii is a protozoan parasite of medical and veterinary significance that is able to infect any warm-blooded vertebrate host. In addition to its importance to public health, several inherent features of the biology of T. gondii have made it an important model organism to study host–pathogen interactions. One factor is the genetic tractability of the parasite, which allows studies on the microbial factors that affect virulence and allows the development of tools that facilitate immune studies. Additionally, mice are natural hosts for T. gondii, and the availability of numerous reagents to study the murine immune system makes this an ideal experimental system to understand the functions of cytokines and effector mechanisms involved in immunity to intracellular microorganisms. In this article, we will review current knowledge of the innate and adaptive immune responses required for resistance to toxoplasmosis, the events that lead to the development of immunopathology, and the natural regulatory mechanisms that limit excessive inflammation during this infection.
Literature
1.
2.
3.
Desmonts G, Couvreur J, Alison F, Baudelot J, Gerbeaux J, Lelong M (1965) Epidemiological study on toxoplasmosis: the influence of cooking slaughter-animal meat on the incidence of human infection. Rev Fr Etud Clin Biol 10(9):952–958PubMed
4.
Kean BH, Kimball AC, Christenson WN (1969) An epidemic of acute toxoplasmosis. Jama 208(6):1002–1004PubMed
5.
Frenkel JK, Dubey JP, Miller NL (1970) Toxoplasma gondii in cats: fecal stages identified as coccidian oocysts. Science 167(3919):893–896PubMed
6.
7.
Johnson LL (1992) SCID mouse models of acute and relapsing chronic Toxoplasma gondii infections. Infect Immun 60(9):3719–3724PubMed
8.
Frenkel JK (1973) Toxoplasma in and around us. BioScience 23(6):343–352
9.
Pappas G, Roussos N, Falagas ME (2009) Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. Int J Parasitol 39(12):1385–1394. doi:10.​1016/​j.​ijpara.​2009.​04.​003 PubMed
10.
11.
Israelski DM, Remington JS (1988) Toxoplasmic encephalitis in patients with AIDS. Infect Dis Clin North Am 2(2):429–445PubMed
12.
Leiva LE, Junprasert J, Hollenbaugh D, Sorensen RU (1998) Central nervous system toxoplasmosis with an increased proportion of circulating gamma delta T cells in a patient with hyper-IgM syndrome. J Clin Immunol 18(4):283–290PubMed
13.
Tsuge I, Matsuoka H, Nakagawa A, Kamachi Y, Aso K, Negoro T, Ito M, Torii S, Watanabe K (1998) Necrotizing toxoplasmic encephalitis in a child with the X-linked hyper-IgM syndrome. Eur J Pediatr 157(9):735–737PubMed
14.
Yong PF, Post FA, Gilmour KC, Grosse-Kreul D, King A, Easterbrook P, Ibrahim MA (2008) Cerebral toxoplasmosis in a middle-aged man as first presentation of primary immunodeficiency due to a hypomorphic mutation in the CD40 ligand gene. J Clin Pathol 61(11):1220–1222. doi:10.​1136/​jcp.​2008.​058362 PubMed
15.
Israelski DM, Remington JS (1993) Toxoplasmosis in patients with cancer. Clin Infect Dis 17(Suppl 2):S423–S435PubMed
16.
17.
Grigg ME, Ganatra J, Boothroyd JC, Margolis TP (2001) Unusual abundance of atypical strains associated with human ocular toxoplasmosis. J Infect Dis 184(5):633–639. doi:10.​1086/​322800 PubMed
18.
Demar M, Ajzenberg D, Maubon D, Djossou F, Panchoe D, Punwasi W, Valery N, Peneau C, Daigre JL, Aznar C, Cottrelle B, Terzan L, Darde ML, Carme B (2007) Fatal outbreak of human toxoplasmosis along the Maroni River: epidemiological, clinical, and parasitological aspects. Clin Infect Dis 45(7):e88–e95. doi:10.​1086/​521246 PubMed
19.
20.
21.
22.
23.
Howe DK, Sibley LD (1995) Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J Infect Dis 172(6):1561–1566PubMed
24.
25.
26.
27.
28.
Bliss SK, Butcher BA, Denkers EY (2000) Rapid recruitment of neutrophils containing prestored IL-12 during microbial infection. J Immunol 165(8):4515–4521PubMed
29.
Tait ED, Jordan KA, Dupont CD, Harris TH, Gregg B, Wilson EH, Pepper M, Dzierszinski F, Roos DS, Hunter CA (2010) Virulence of Toxoplasma gondii is associated with distinct dendritic cell responses and reduced numbers of activated CD8+ T cells. J Immunol 185(3):1502–1512. doi:10.​4049/​jimmunol.​0903450 PubMed
30.
Dunay IR, Fuchs A, Sibley LD (2010) Inflammatory monocytes but not neutrophils are necessary to control infection with Toxoplasma gondii in mice. Infect Immun 78(4):1564–1570. doi:10.​1128/​IAI.​00472-09 PubMed
31.
Del Rio L, Bennouna S, Salinas J, Denkers EY (2001) CXCR2 deficiency confers impaired neutrophil recruitment and increased susceptibility during Toxoplasma gondii infection. J Immunol 167(11):6503–6509PubMed
32.
Liu CH, Fan YT, Dias A, Esper L, Corn RA, Bafica A, Machado FS, Aliberti J (2006) Cutting edge: dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice. J Immunol 177(1):31–35PubMed
33.
Gazzinelli RT, Hieny S, Wynn TA, Wolf S, Sher A (1993) Interleukin 12 is required for the T-lymphocyte-independent induction of interferon gamma by an intracellular parasite and induces resistance in T-cell-deficient hosts. Proc Natl Acad Sci U S A 90(13):6115–6119PubMed
34.
Gazzinelli RT, Wysocka M, Hayashi S, Denkers EY, Hieny S, Caspar P, Trinchieri G, Sher A (1994) Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii. J Immunol 153(6):2533–2543PubMed
35.
Hunter CA, Subauste CS, Van Cleave VH, Remington JS (1994) Production of gamma interferon by natural killer cells from Toxoplasma gondii-infected SCID mice: regulation by interleukin-10, interleukin-12, and tumor necrosis factor alpha. Infect Immun 62(7):2818–2824PubMed
36.
Suzuki Y, Orellana MA, Schreiber RD, Remington JS (1988) Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science 240(4851):516–518PubMed
37.
Scanga CA, Aliberti J, Jankovic D, Tilloy F, Bennouna S, Denkers EY, Medzhitov R, Sher A (2002) Cutting edge: MyD88 is required for resistance to Toxoplasma gondii infection and regulates parasite-induced IL-12 production by dendritic cells. J Immunol 168(12):5997–6001PubMed
38.
Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, Hieny S, Sutterwala FS, Flavell RA, Ghosh S, Sher A (2005) TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308(5728):1626–1629. doi:10.​1126/​science.​1109893 PubMed
39.
40.
Debierre-Grockiego F, Campos MA, Azzouz N, Schmidt J, Bieker U, Resende MG, Mansur DS, Weingart R, Schmidt RR, Golenbock DT, Gazzinelli RT, Schwarz RT (2007) Activation of TLR2 and TLR4 by glycosylphosphatidylinositols derived from Toxoplasma gondii. J Immunol 179(2):1129–1137PubMed
41.
42.
Sukhumavasi W, Egan CE, Warren AL, Taylor GA, Fox BA, Bzik DJ, Denkers EY (2008) TLR adaptor MyD88 is essential for pathogen control during oral Toxoplasma gondii infection but not adaptive immunity induced by a vaccine strain of the parasite. J Immunol 181(5):3464–3473PubMed
43.
Bliss SK, Marshall AJ, Zhang Y, Denkers EY (1999) Human polymorphonuclear leukocytes produce IL-12, TNF-alpha, and the chemokines macrophage-inflammatory protein-1 alpha and -1 beta in response to Toxoplasma gondii antigens. J Immunol 162(12):7369–7375PubMed
44.
Gazzinelli RT, Wysocka M, Hieny S, Scharton-Kersten T, Cheever A, Kuhn R, Muller W, Trinchieri G, Sher A (1996) In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. J Immunol 157(2):798–805PubMed
45.
46.
Hou B, Benson A, Kuzmich L, DeFranco AL, Yarovinsky F (2011) Critical coordination of innate immune defense against Toxoplasma gondii by dendritic cells responding via their toll-like receptors. Proc Natl Acad Sci U S A 108(1):278–283. doi:10.​1073/​pnas.​1011549108 PubMed
47.
Reise Sousa C, Hieny S, Scharton-Kersten T, Jankovic D, Charest H, Germain RN, Sher A (1997) In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas. J Exp Med 186(11):1819–1829
48.
Mashayekhi M, Sandau MM, Dunay IR, Frickel EM, Khan A, Goldszmid RS, Sher A, Ploegh HL, Murphy TL, Sibley LD, Murphy KM (2011) CD8alpha(+) dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites. Immunity 35(2):249–259. doi:10.​1016/​j.​immuni.​2011.​08.​008 PubMed
49.
Bliss SK, Zhang Y, Denkers EY (1999) Murine neutrophil stimulation by Toxoplasma gondii antigen drives high level production of IFN-gamma-independent IL-12. J Immunol 163(4):2081–2088PubMed
50.
51.
Nakao M, Konishi E (1991) Proliferation of Toxoplasma gondii in human neutrophils in vitro. Parasitology 103(Pt 1):23–27PubMed
52.
Konishi E, Nakao M (1992) Naturally occurring immunoglobulin M antibodies: enhancement of phagocytic and microbicidal activities of human neutrophils against Toxoplasma gondii. Parasitology 104(Pt 3):427–432PubMed
53.
Chtanova T, Schaeffer M, Han SJ, van Dooren GG, Nollmann M, Herzmark P, Chan SW, Satija H, Camfield K, Aaron H, Striepen B, Robey EA (2008) Dynamics of neutrophil migration in lymph nodes during infection. Immunity 29(3):487–496. doi:10.​1016/​j.​immuni.​2008.​07.​012 PubMed
54.
Abi Abdallah DS, Lin C, Ball CJ, King MR, Duhamel GE, Denkers EY (2012) Toxoplasma gondii triggers release of human and mouse neutrophil extracellular traps. Infect Immun 80(2):768–777. doi:10.​1128/​IAI.​05730-11 PubMed
55.
Egan CE, Sukhumavasi W, Bierly AL, Denkers EY (2008) Understanding the multiple functions of Gr-1(+) cell subpopulations during microbial infection. Immunol Res 40(1):35–48. doi:10.​1007/​s12026-007-0061-8 PubMed
56.
Alexander J, Scharton-Kersten TM, Yap G, Roberts CW, Liew FY, Sher A (1997) Mechanisms of innate resistance to Toxoplasma gondii infection. Philos Trans R Soc Lond B Biol Sci 352(1359):1355–1359. doi:10.​1098/​rstb.​1997.​0120 PubMed
57.
Robben PM, LaRegina M, Kuziel WA, Sibley LD (2005) Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis. J Exp Med 201(11):1761–1769. doi:10.​1084/​jem.​20050054 PubMed
58.
Benevides L, Milanezi CM, Yamauchi LM, Benjamim CF, Silva JS, Silva NM (2008) CCR2 receptor is essential to activate microbicidal mechanisms to control Toxoplasma gondii infection in the central nervous system. Am J Pathol 173(3):741–751. doi:10.​2353/​ajpath.​2008.​080129 PubMed
59.
Aldebert D, Durand F, Mercier C, Brenier-Pinchart MP, Cesbron-Delauw MF, Pelloux H (2007) Toxoplasma gondii triggers secretion of interleukin-12 but low level of interleukin-10 from the THP-1 human monocytic cell line. Cytokine 37(3):206–211. doi:10.​1016/​j.​cyto.​2007.​03.​012 PubMed
60.
61.
Borges JS, Johnson WD Jr (1975) Inhibition of multiplication of Toxoplasma gondii by human monocytes exposed to T-lymphocyte products. J Exp Med 141(2):483–496PubMed
62.
Wilson CB, Remington JS (1979) Activity of human blood leukocytes against Toxoplasma gondii. J Infect Dis 140(6):890–895PubMed
63.
Scharton-Kersten TM, Yap G, Magram J, Sher A (1997) Inducible nitric oxide is essential for host control of persistent but not acute infection with the intracellular pathogen Toxoplasma gondii. J Exp Med 185(7):1261–1273PubMed
64.
Gazzinelli RT, Bala S, Stevens R, Baseler M, Wahl L, Kovacs J, Sher A (1995) HIV infection suppresses type 1 lymphokine and IL-12 responses to Toxoplasma gondii but fails to inhibit the synthesis of other parasite-induced monokines. J Immunol 155(3):1565–1574PubMed
65.
Hammouda NA, Rashwan EA, Hussien ED, Abo el-Naga I, Fathy FM (1995) Measurement of respiratory burst of TNF and IL-1 cytokine activated murine peritoneal macrophages challenged with Toxoplasma gondii. J Egypt Soc Parasitol 25(3):683–691PubMed
66.
Halonen SK, Chiu F, Weiss LM (1998) Effect of cytokines on growth of Toxoplasma gondii in murine astrocytes. Infect Immun 66(10):4989–4993PubMed
67.
Hunter CA, Chizzonite R, Remington JS (1995) IL-1 beta is required for IL-12 to induce production of IFN-gamma by NK cells. A role for IL-1 beta in the T cell-independent mechanism of resistance against intracellular pathogens. J Immunol 155(9):4347–4354PubMed
68.
Shibuya K, Robinson D, Zonin F, Hartley SB, Macatonia SE, Somoza C, Hunter CA, Murphy KM, O'Garra A (1998) IL-1 alpha and TNF-alpha are required for IL-12-induced development of Th1 cells producing high levels of IFN-gamma in BALB/c but not C57BL/6 mice. J Immunol 160(4):1708–1716PubMed
69.
70.
Johnson LL, VanderVegt FP, Havell EA (1993) Gamma interferon-dependent temporary resistance to acute Toxoplasma gondii infection independent of CD4+ or CD8+ lymphocytes. Infect Immun 61(12):5174–5180PubMed
71.
Sher A, Oswald IP, Hieny S, Gazzinelli RT (1993) Toxoplasma gondii induces a T-independent IFN-gamma response in natural killer cells that requires both adherent accessory cells and tumor necrosis factor-alpha. J Immunol 150(9):3982–3989PubMed
72.
Denkers EY, Gazzinelli RT, Martin D, Sher A (1993) Emergence of NK1.1+ cells as effectors of IFN-gamma dependent immunity to Toxoplasma gondii in MHC class I-deficient mice. J Exp Med 178(5):1465–1472PubMed
73.
Hauser WE Jr, Sharma SD, Remington JS (1982) Natural killer cells induced by acute and chronic toxoplasma infection. Cell Immunol 69(2):330–346PubMed
74.
75.
Perona-Wright G, Mohrs K, Szaba FM, Kummer LW, Madan R, Karp CL, Johnson LL, Smiley ST, Mohrs M (2009) Systemic but not local infections elicit immunosuppressive IL-10 production by natural killer cells. Cell Host Microbe 6(6):503–512. doi:10.​1016/​j.​chom.​2009.​11.​003 PubMed
76.
Subauste CS, Dawson L, Remington JS (1992) Human lymphokine-activated killer cells are cytotoxic against cells infected with Toxoplasma gondii. J Exp Med 176(6):1511–1519PubMed
77.
Hauser WE Jr, Tsai V (1986) Acute toxoplasma infection of mice induces spleen NK cells that are cytotoxic for T. gondii in vitro. J Immunol 136(1):313–319PubMed
78.
Persson CM, Lambert H, Vutova PP, Dellacasa-Lindberg I, Nederby J, Yagita H, Ljunggren HG, Grandien A, Barragan A, Chambers BJ (2009) Transmission of Toxoplasma gondii from infected dendritic cells to natural killer cells. Infect Immun 77(3):970–976. doi:10.​1128/​IAI.​00833-08 PubMed
79.
80.
Guan H, Moretto M, Bzik DJ, Gigley J, Khan IA (2007) NK cells enhance dendritic cell response against parasite antigens via NKG2D pathway. J Immunol 179(1):590–596PubMed
81.
Goldszmid RS, Bafica A, Jankovic D, Feng CG, Caspar P, Winkler-Pickett R, Trinchieri G, Sher A (2007) TAP-1 indirectly regulates CD4+ T cell priming in Toxoplasma gondii infection by controlling NK cell IFN-gamma production. J Exp Med 204(11):2591–2602. doi:10.​1084/​jem.​20070634 PubMed
82.
Kang H, Remington JS, Suzuki Y (2000) Decreased resistance of B cell-deficient mice to infection with Toxoplasma gondii despite unimpaired expression of IFN-gamma, TNF-alpha, and inducible nitric oxide synthase. J Immunol 164(5):2629–2634PubMed
83.
Johnson LL, Sayles PC (2002) Deficient humoral responses underlie susceptibility to Toxoplasma gondii in CD4-deficient mice. Infect Immun 70(1):185–191PubMed
84.
Denkers EY, Yap G, Scharton-Kersten T, Charest H, Butcher BA, Caspar P, Heiny S, Sher A (1997) Perforin-mediated cytolysis plays a limited role in host resistance to Toxoplasma gondii. J Immunol 159(4):1903–1908PubMed
85.
86.
Blanchard N, Gonzalez F, Schaeffer M, Joncker NT, Cheng T, Shastri AJ, Robey EA, Shastri N (2008) Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum. Nat Immunol 9(8):937–944. doi:10.​1038/​ni.​1629 PubMed
87.
John B, Weninger W, Hunter CA (2010) Advances in imaging the innate and adaptive immune response to Toxoplasma gondii. Future Microbiol 5(9):1321–1328. doi:10.​2217/​fmb.​10.​97 PubMed
88.
Luft BJ, Brooks RG, Conley FK, McCabe RE, Remington JS (1984) Toxoplasmic encephalitis in patients with acquired immune deficiency syndrome. Jama 252(7):913–917PubMed
89.
Lutjen S, Soltek S, Virna S, Deckert M, Schluter D (2006) Organ- and disease-stage-specific regulation of Toxoplasma gondii-specific CD8-T-cell responses by CD4 T cells. Infect Immun 74(10):5790–5801. doi:10.​1128/​IAI.​00098-06 PubMed
90.
Gazzinelli R, Xu Y, Hieny S, Cheever A, Sher A (1992) Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii. J Immunol 149(1):175–180PubMed
91.
Reichmann G, Walker W, Villegas EN, Craig L, Cai G, Alexander J, Hunter CA (2000) The CD40/CD40 ligand interaction is required for resistance to toxoplasmic encephalitis. Infect Immun 68(3):1312–1318PubMed
92.
Andrade RM, Portillo JA, Wessendarp M, Subauste CS (2005) CD40 signaling in macrophages induces activity against an intracellular pathogen independently of gamma interferon and reactive nitrogen intermediates. Infect Immun 73(5):3115–3123. doi:10.​1128/​IAI.​73.​5.​3115-3123.​2005 PubMed
93.
94.
Subauste CS, Andrade RM, Wessendarp M (2007) CD40-TRAF6 and autophagy-dependent anti-microbial activity in macrophages. Autophagy 3(3):245–248PubMed
95.
Portillo JA, Okenka G, Reed E, Subauste A, Van Grol J, Gentil K, Komatsu M, Tanaka K, Landreth G, Levine B, Subauste CS (2010) The CD40-autophagy pathway is needed for host protection despite IFN-Gamma-dependent immunity and CD40 induces autophagy via control of P21 levels. PLoS One 5(12):e14472. doi:10.​1371/​journal.​pone.​0014472 PubMed
96.
97.
Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP (1992) CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 356(6370):607–609. doi:10.​1038/​356607a0 PubMed
98.
Curtsinger JM, Schmidt CS, Mondino A, Lins DC, Kedl RM, Jenkins MK, Mescher MF (1999) Inflammatory cytokines provide a third signal for activation of naive CD4+ and CD8+ T cells. J Immunol 162(6):3256–3262PubMed
99.
Curtsinger JM, Johnson CM, Mescher MF (2003) CD8 T cell clonal expansion and development of effector function require prolonged exposure to antigen, costimulation, and signal 3 cytokine. J Immunol 171(10):5165–5171PubMed
100.
Villegas EN, Lieberman LA, Mason N, Blass SL, Zediak VP, Peach R, Horan T, Yoshinaga S, Hunter CA (2002) A role for inducible costimulator protein in the CD28- independent mechanism of resistance to Toxoplasma gondii. J Immunol 169(2):937–943PubMed
101.
Wilson DC, Matthews S, Yap GS (2008) IL-12 signaling drives CD8+ T cell IFN-gamma production and differentiation of KLRG1+ effector subpopulations during Toxoplasma gondii infection. J Immunol 180(9):5935–5945PubMed
102.
103.
Jung S, Unutmaz D, Wong P, Sano G, De los Santos K, Sparwasser T, Wu S, Vuthoori S, Ko K, Zavala F, Pamer EG, Littman DR, Lang RA (2002) In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity 17(2):211–220PubMed
104.
Takagi H, Fukaya T, Eizumi K, Sato Y, Sato K, Shibazaki A, Otsuka H, Hijikata A, Watanabe T, Ohara O, Kaisho T, Malissen B (2011) Plasmacytoid dendritic cells are crucial for the initiation of inflammation and T cell immunity in vivo. Immunity 35(6):958–971. doi:10.​1016/​j.​immuni.​2011.​10.​014 PubMed
105.
McKee AS, Dzierszinski F, Boes M, Roos DS, Pearce EJ (2004) Functional inactivation of immature dendritic cells by the intracellular parasite Toxoplasma gondii. J Immunol 173(4):2632–2640PubMed
106.
Lang C, Algner M, Beinert N, Gross U, Luder CG (2006) Diverse mechanisms employed by Toxoplasma gondii to inhibit IFN-gamma-induced major histocompatibility complex class II gene expression. Microbes Infect 8(8):1994–2005. doi:10.​1016/​j.​micinf.​2006.​02.​031 PubMed
107.
108.
Goldszmid RS, Coppens I, Lev A, Caspar P, Mellman I, Sher A (2009) Host ER-parasitophorous vacuole interaction provides a route of entry for antigen cross-presentation in Toxoplasma gondii-infected dendritic cells. J Exp Med 206(2):399–410. doi:10.​1084/​jem.​20082108 PubMed
109.
Koshy AA, Fouts AE, Lodoen MB, Alkan O, Blau HM, Boothroyd JC (2010) Toxoplasma secreting Cre recombinase for analysis of host–parasite interactions. Nat Methods 7(4):307–309. doi:10.​1038/​nmeth.​1438 PubMed
110.
Subauste CS, de Waal Malefyt R, Fuh F (1998) Role of CD80 (B7.1) and CD86 (B7.2) in the immune response to an intracellular pathogen. J Immunol 160(4):1831–1840PubMed
111.
Subauste CS, Wessendarp M (2000) Human dendritic cells discriminate between viable and killed Toxoplasma gondii tachyzoites: dendritic cell activation after infection with viable parasites results in CD28 and CD40 ligand signaling that controls IL-12-dependent and -independent T cell production of IFN-gamma. J Immunol 165(3):1498–1505PubMed
112.
113.
Correa D, Canedo-Solares I, Ortiz-Alegria LB, Caballero-Ortega H, Rico-Torres CP (2007) Congenital and acquired toxoplasmosis: diversity and role of antibodies in different compartments of the host. Parasite Immunol 29(12):651–660. doi:10.​1111/​j.​1365-3024.​2007.​00982.​x PubMed
114.
Remington JS, Miller MJ, Brownlee I (1968) IgM antibodies in acute toxoplasmosis. II. Prevalence and significance in acquired cases. J Lab Clin Med 71(5):855–866PubMed
115.
Remington JS (1969) The present status of the IgM fluorescent antibody technique in the diagnosis of congenital toxoplasmosis. J Pediatr 75(6):1116–1124PubMed
116.
Remington JS, Thulliez P, Montoya JG (2004) Recent developments for diagnosis of toxoplasmosis. J Clin Microbiol 42(3):941–945PubMed
117.
Erbe DV, Pfefferkorn ER, Fanger MW (1991) Functions of the various IgG Fc receptors in mediating killing of Toxoplasma gondii. J Immunol 146(9):3145–3151PubMed
118.
Hammouda NA, Abo el-Naga I, Hussein ED, Rashwan EA (1995) Opsonization and intracellular killing of Toxoplasma gondii by human mononuclear phagocytes. J Egypt Soc Parasitol 25(1):11–17PubMed
119.
Vercammen M, Scorza T, El Bouhdidi A, Van Beeck K, Carlier Y, Dubremetz JF, Verschueren H (1999) Opsonization of Toxoplasma gondii tachyzoites with nonspecific immunoglobulins promotes their phagocytosis by macrophages and inhibits their proliferation in nonphagocytic cells in tissue culture. Parasite Immunol 21(11):555–563PubMed
120.
Suzuki M, Tsunematsu Y (1971) Studies on the accessory factor for the toxoplasma dye test: essential role of complement. J Parasitol 57(4):924–925PubMed
121.
Schreiber RD, Feldman HA (1980) Identification of the activator system for antibody to Toxoplasma as the classical complement pathway. J Infect Dis 141(3):366–369PubMed
122.
Johnson LL, Gibson GW, Sayles PC (1996) CR3-dependent resistance to acute Toxoplasma gondii infection in mice. Infect Immun 64(6):1998–2003PubMed
123.
Glatman Zaretsky A, Silver JS, Siwicki M, Durham A, Ware CF, Hunter CA (2012) Infection with Toxoplasma gondii alters lymphotoxin expression associated with changes in splenic architecture. Infect Immun. doi:10.​1128/​IAI.​00333-12
124.
John B, Harris TH, Tait ED, Wilson EH, Gregg B, Ng LG, Mrass P, Roos DS, Dzierszinski F, Weninger W, Hunter CA (2009) Dynamic imaging of CD8(+) T cells and dendritic cells during infection with Toxoplasma gondii. PLoS Pathog 5(7):e1000505. doi:10.​1371/​journal.​ppat.​1000505 PubMed
125.
Vinuesa CG, Tangye SG, Moser B, Mackay CR (2005) Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 5(11):853–865. doi:10.​1038/​nri1714 PubMed
126.
127.
Cadman ET, Abdallah AY, Voisine C, Sponaas AM, Corran P, Lamb T, Brown D, Ndungu F, Langhorne J (2008) Alterations of splenic architecture in malaria are induced independently of toll-like receptors 2, 4, and 9 or MyD88 and may affect antibody affinity. Infect Immun 76(9):3924–3931. doi:10.​1128/​IAI.​00372-08 PubMed
128.
Odermatt B, Eppler M, Leist TP, Hengartner H, Zinkernagel RM (1991) Virus-triggered acquired immunodeficiency by cytotoxic T-cell-dependent destruction of antigen-presenting cells and lymph follicle structure. Proc Natl Acad Sci U S A 88(18):8252–8256PubMed
129.
Racine R, Jones DD, Chatterjee M, McLaughlin M, Macnamara KC, Winslow GM (2010) Impaired germinal center responses and suppression of local IgG production during intracellular bacterial infection. J Immunol 184(9):5085–5093. doi:10.​4049/​jimmunol.​0902710 PubMed
130.
Scandella E, Bolinger B, Lattmann E, Miller S, Favre S, Littman DR, Finke D, Luther SA, Junt T, Ludewig B (2008) Restoration of lymphoid organ integrity through the interaction of lymphoid tissue-inducer cells with stroma of the T cell zone. Nat Immunol 9(6):667–675. doi:10.​1038/​ni.​1605 PubMed
131.
St John AL, Abraham SN (2009) Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines. Nat Med 15(11):1259–1265. doi:10.​1038/​nm.​2036 PubMed
132.
Parker SJ, Roberts CW, Alexander J (1991) CD8+ T cells are the major lymphocyte subpopulation involved in the protective immune response to Toxoplasma gondii in mice. Clin Exp Immunol 84(2):207–212PubMed
133.
Gigley JP, Fox BA, Bzik DJ (2009) Cell-mediated immunity to Toxoplasma gondii develops primarily by local Th1 host immune responses in the absence of parasite replication. J Immunol 182(2):1069–1078PubMed
134.
Khan IA, Smith KA, Kasper LH (1988) Induction of antigen-specific parasiticidal cytotoxic T cell splenocytes by a major membrane protein (P30) of Toxoplasma gondii. J Immunol 141(10):3600–3605PubMed
135.
Frickel EM, Sahoo N, Hopp J, Gubbels MJ, Craver MP, Knoll LJ, Ploegh HL, Grotenbreg GM (2008) Parasite stage-specific recognition of endogenous Toxoplasma gondii-derived CD8+ T cell epitopes. J Infect Dis 198(11):1625–1633. doi:10.​1086/​593019 PubMed
136.
Wilson DC, Grotenbreg GM, Liu K, Zhao Y, Frickel EM, Gubbels MJ, Ploegh HL, Yap GS (2010) Differential regulation of effector- and central-memory responses to Toxoplasma gondii infection by IL-12 revealed by tracking of Tgd057-specific CD8+ T cells. PLoS Pathog 6(3):e1000815. doi:10.​1371/​journal.​ppat.​1000815 PubMed
137.
Kwok LY, Lutjen S, Soltek S, Soldati D, Busch D, Deckert M, Schluter D (2003) The induction and kinetics of antigen-specific CD8 T cells are defined by the stage specificity and compartmentalization of the antigen in murine toxoplasmosis. J Immunol 170(4):1949–1957PubMed
138.
Pepper M, Dzierszinski F, Crawford A, Hunter CA, Roos D (2004) Development of a system to study CD4 + -T-cell responses to transgenic ovalbumin-expressing Toxoplasma gondii during toxoplasmosis. Infect Immun 72(12):7240–7246. doi:10.​1128/​IAI.​72.​12.​7240-7246.​2004 PubMed
139.
140.
Chtanova T, Han SJ, Schaeffer M, van Dooren GG, Herzmark P, Striepen B, Robey EA (2009) Dynamics of T cell, antigen-presenting cell, and pathogen interactions during recall responses in the lymph node. Immunity 31(2):342–355. doi:10.​1016/​j.​immuni.​2009.​06.​023 PubMed
141.
Dzierszinski F, Pepper M, Stumhofer JS, LaRosa DF, Wilson EH, Turka LA, Halonen SK, Hunter CA, Roos DS (2007) Presentation of Toxoplasma gondii antigens via the endogenous major histocompatibility complex class I pathway in nonprofessional and professional antigen-presenting cells. Infect Immun 75(11):5200–5209. doi:10.​1128/​IAI.​00954-07 PubMed
142.
Gubbels MJ, Striepen B, Shastri N, Turkoz M, Robey EA (2005) Class I major histocompatibility complex presentation of antigens that escape from the parasitophorous vacuole of Toxoplasma gondii. Infect Immun 73(2):703–711. doi:10.​1128/​IAI.​73.​2.​703-711.​2005 PubMed
143.
Lin ML, Zhan Y, Villadangos JA, Lew AM (2008) The cell biology of cross-presentation and the role of dendritic cell subsets. Immunol Cell Biol 86(4):353–362. doi:10.​1038/​icb.​2008.​3 PubMed
144.
Denkers EY, Scharton-Kersten T, Barbieri S, Caspar P, Sher A (1996) A role for CD4+ NK1.1+ T lymphocytes as major histocompatibility complex class II independent helper cells in the generation of CD8+ effector function against intracellular infection. J Exp Med 184(1):131–139PubMed
145.
Jordan KA, Wilson EH, Tait ED, Fox BA, Roos DS, Bzik DJ, Dzierszinski F, Hunter CA (2009) Kinetics and phenotype of vaccine-induced CD8+ T-cell responses to Toxoplasma gondii. Infect Immun 77(9):3894–3901. doi:10.​1128/​IAI.​00024-09 PubMed
146.
147.
Yamamoto M, Takeda K (2012) Inhibition of ATF6beta-dependent host adaptive immune response by a Toxoplasma virulence factor ROP18. Virulence 3(1)
148.
Jordan KA, Dupont CD, Tait ED, Liou HC, Hunter CA (2010) Role of the NF-kappaB transcription factor c-Rel in the generation of CD8+ T-cell responses to Toxoplasma gondii. Int Immunol 22(11):851–861. doi:10.​1093/​intimm/​dxq439 PubMed
149.
Brown CR, Hunter CA, Estes RG, Beckmann E, Forman J, David C, Remington JS, McLeod R (1995) Definitive identification of a gene that confers resistance against Toxoplasma cyst burden and encephalitis. Immunology 85(3):419–428PubMed
150.
Suzuki Y, Joh K, Kwon OC, Yang Q, Conley FK, Remington JS (1994) MHC class I gene(s) in the D/L region but not the TNF-alpha gene determines development of toxoplasmic encephalitis in mice. J Immunol 153(10):4649–4654PubMed
151.
Rosenberg CS, Martin DL, Tarleton RL (2010) CD8+ T cells specific for immunodominant trans-sialidase epitopes contribute to control of Trypanosoma cruzi infection but are not required for resistance. J Immunol 185(1):560–568. doi:10.​4049/​jimmunol.​1000432 PubMed
152.
Deckert-Schluter M, Bluethmann H, Rang A, Hof H, Schluter D (1998) Crucial role of TNF receptor type 1 (p55), but not of TNF receptor type 2 (p75), in murine toxoplasmosis. J Immunol 160(7):3427–3436PubMed
153.
Yap GS, Scharton-Kersten T, Charest H, Sher A (1998) Decreased resistance of TNF receptor p55- and p75-deficient mice to chronic toxoplasmosis despite normal activation of inducible nitric oxide synthase in vivo. J Immunol 160(3):1340–1345PubMed
154.
Schluter D, Kwok LY, Lutjen S, Soltek S, Hoffmann S, Korner H, Deckert M (2003) Both lymphotoxin-alpha and TNF are crucial for control of Toxoplasma gondii in the central nervous system. J Immunol 170(12):6172–6182PubMed
155.
Nathan CF, Murray HW, Wiebe ME, Rubin BY (1983) Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158(3):670–689PubMed
156.
Adams LB, Hibbs JB Jr, Taintor RR, Krahenbuhl JL (1990) Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. J Immunol 144(7):2725–2729PubMed
157.
Koide M, Kawahara Y, Tsuda T, Yokoyama M (1993) Cytokine-induced expression of an inducible type of nitric oxide synthase gene in cultured vascular smooth muscle cells. FEBS Lett 318(3):213–217PubMed
158.
Langermans JA, Van der Hulst ME, Nibbering PH, Hiemstra PS, Fransen L, Van Furth R (1992) IFN-gamma-induced L-arginine-dependent toxoplasmastatic activity in murine peritoneal macrophages is mediated by endogenous tumor necrosis factor-alpha. J Immunol 148(2):568–574PubMed
159.
Chao CC, Anderson WR, Hu S, Gekker G, Martella A, Peterson PK (1993) Activated microglia inhibit multiplication of Toxoplasma gondii via a nitric oxide mechanism. Clin Immunol Immunopathol 67(2):178–183PubMed
160.
Jun CD, Kim SH, Soh CT, Kang SS, Chung HT (1993) Nitric oxide mediates the toxoplasmastatic activity of murine microglial cells in vitro. Immunol Invest 22(8):487–501PubMed
161.
Zhao Y, Ferguson DJ, Wilson DC, Howard JC, Sibley LD, Yap GS (2009) Virulent Toxoplasma gondii evade immunity-related GTPase-mediated parasite vacuole disruption within primed macrophages. J Immunol 182(6):3775–3781. doi:10.​4049/​jimmunol.​0804190 PubMed
162.
Jana M, Liu X, Koka S, Ghosh S, Petro TM, Pahan K (2001) Ligation of CD40 stimulates the induction of nitric-oxide synthase in microglial cells. J Biol Chem 276(48):44527–44533. doi:10.​1074/​jbc.​M106771200 PubMed
163.
Hayashi S, Chan CC, Gazzinelli R, Roberge FG (1996) Contribution of nitric oxide to the host parasite equilibrium in toxoplasmosis. J Immunol 156(4):1476–1481PubMed
164.
Chakravortty D, Hensel M (2003) Inducible nitric oxide synthase and control of intracellular bacterial pathogens. Microbes Infect 5(7):621–627PubMed
165.
Taylor GA, Jeffers M, Largaespada DA, Jenkins NA, Copeland NG, Woude GF (1996) Identification of a novel GTPase, the inducibly expressed GTPase, that accumulates in response to interferon gamma. J Biol Chem 271(34):20399–20405PubMed
166.
167.
Taylor GA, Collazo CM, Yap GS, Nguyen K, Gregorio TA, Taylor LS, Eagleson B, Secrest L, Southon EA, Reid SW, Tessarollo L, Bray M, McVicar DW, Komschlies KL, Young HA, Biron CA, Sher A, Vande Woude GF (2000) Pathogen-specific loss of host resistance in mice lacking the IFN-gamma-inducible gene IGTP. Proc Natl Acad Sci U S A 97(2):751–755PubMed
168.
Collazo CM, Yap GS, Sempowski GD, Lusby KC, Tessarollo L, Woude GF, Sher A, Taylor GA (2001) Inactivation of LRG-47 and IRG-47 reveals a family of interferon gamma-inducible genes with essential, pathogen-specific roles in resistance to infection. J Exp Med 194(2):181–188PubMed
169.
Pawlowski N, Khaminets A, Hunn JP, Papic N, Schmidt A, Uthaiah RC, Lange R, Vopper G, Martens S, Wolf E, Howard JC (2011) The activation mechanism of Irga6, an interferon-inducible GTPase contributing to mouse resistance against Toxoplasma gondii. BMC Biol 9:7. doi:10.​1186/​1741-7007-9-7 PubMed
170.
Fentress SJ, Behnke MS, Dunay IR, Mashayekhi M, Rommereim LM, Fox BA, Bzik DJ, Taylor GA, Turk BE, Lichti CF, Townsend RR, Qiu W, Hui R, Beatty WL, Sibley LD (2010) Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence. Cell Host Microbe 8(6):484–495. doi:10.​1016/​j.​chom.​2010.​11.​005 PubMed
171.
Martens S, Parvanova I, Zerrahn J, Griffiths G, Schell G, Reichmann G, Howard JC (2005) Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases. PLoS pathogens 1(3):e24. doi:10.​1371/​journal.​ppat.​0010024 PubMed
172.
Ling YM, Shaw MH, Ayala C, Coppens I, Taylor GA, Ferguson DJ, Yap GS (2006) Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages. J Exp Med 203(9):2063–2071. doi:10.​1084/​jem.​20061318 PubMed
173.
Hunn JP, Koenen-Waisman S, Papic N, Schroeder N, Pawlowski N, Lange R, Kaiser F, Zerrahn J, Martens S, Howard JC (2008) Regulatory interactions between IRG resistance GTPases in the cellular response to Toxoplasma gondii. EMBO J 27(19):2495–2509. doi:10.​1038/​emboj.​2008.​176 PubMed
174.
Zhao Z, Fux B, Goodwin M, Dunay IR, Strong D, Miller BC, Cadwell K, Delgado MA, Ponpuak M, Green KG, Schmidt RE, Mizushima N, Deretic V, Sibley LD, Virgin HW (2008) Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. Cell Host Microbe 4(5):458–469. doi:10.​1016/​j.​chom.​2008.​10.​003 PubMed
175.
Zhao YO, Khaminets A, Hunn JP, Howard JC (2009) Disruption of the Toxoplasma gondii parasitophorous vacuole by IFNgamma-inducible immunity-related GTPases (IRG proteins) triggers necrotic cell death. PLoS pathogens 5(2):e1000288. doi:10.​1371/​journal.​ppat.​1000288 PubMed
176.
Khaminets A, Hunn JP, Konen-Waisman S, Zhao YO, Preukschat D, Coers J, Boyle JP, Ong YC, Boothroyd JC, Reichmann G, Howard JC (2010) Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole. Cell Microbiol 12(7):939–961. doi:10.​1111/​j.​1462-5822.​2010.​01443.​x PubMed
177.
Steinfeldt T, Konen-Waisman S, Tong L, Pawlowski N, Lamkemeyer T, Sibley LD, Hunn JP, Howard JC (2010) Phosphorylation of mouse immunity-related GTPase (IRG) resistance proteins is an evasion strategy for virulent Toxoplasma gondii. PLoS Biol 8(12):e1000576. doi:10.​1371/​journal.​pbio.​1000576 PubMed
178.
Melzer T, Duffy A, Weiss LM, Halonen SK (2008) The gamma interferon (IFN-gamma)-inducible GTP-binding protein IGTP is necessary for toxoplasma vacuolar disruption and induces parasite egression in IFN-gamma-stimulated astrocytes. Infect Immun 76(11):4883–4894. doi:10.​1128/​IAI.​01288-07 PubMed
179.
Virreira Winter S, Niedelman W, Jensen KD, Rosowski EE, Julien L, Spooner E, Caradonna K, Burleigh BA, Saeij JP, Ploegh HL, Frickel EM (2011) Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it. PLoS One 6(9):e24434. doi:10.​1371/​journal.​pone.​0024434 PubMed
180.
Kim BH, Shenoy AR, Kumar P, Das R, Tiwari S, MacMicking JD (2011) A family of IFN-gamma-inducible 65-kD GTPases protects against bacterial infection. Science 332(6030):717–721. doi:10.​1126/​science.​1201711 PubMed
181.
Pfefferkorn ER (1984) Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. Proc Natl Acad Sci U S A 81(3):908–912PubMed
182.
Murray HW, Szuro-Sudol A, Wellner D, Oca MJ, Granger AM, Libby DM, Rothermel CD, Rubin BY (1989) Role of tryptophan degradation in respiratory burst-independent antimicrobial activity of gamma interferon-stimulated human macrophages. Infect Immun 57(3):845–849PubMed
183.
Daubener W, Remscheid C, Nockemann S, Pilz K, Seghrouchni S, Mackenzie C, Hadding U (1996) Anti-parasitic effector mechanisms in human brain tumor cells: role of interferon-gamma and tumor necrosis factor-alpha. Eur J Immunol 26(2):487–492. doi:10.​1002/​eji.​1830260231 PubMed
184.
Daubener W, Spors B, Hucke C, Adam R, Stins M, Kim KS, Schroten H (2001) Restriction of Toxoplasma gondii growth in human brain microvascular endothelial cells by activation of indoleamine 2,3-dioxygenase. Infect Immun 69(10):6527–6531. doi:10.​1128/​IAI.​69.​10.​6527-6531.​2001 PubMed
185.
Metz R, Duhadaway JB, Kamasani U, Laury-Kleintop L, Muller AJ, Prendergast GC (2007) Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res 67(15):7082–7087. doi:10.​1158/​0008-5472.​CAN-07-1872 PubMed
186.
Sibley LD, Messina M, Niesman IR (1994) Stable DNA transformation in the obligate intracellular parasite Toxoplasma gondii by complementation of tryptophan auxotrophy. Proc Natl Acad Sci U S A 91(12):5508–5512PubMed
187.
Divanovic S, Sawtell NM, Trompette A, Warning JI, Dias A, Cooper AM, Yap GS, Arditi M, Shimada K, Duhadaway JB, Prendergast GC, Basaraba RJ, Mellor AL, Munn DH, Aliberti J, Karp CL (2012) Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection. J Infect Dis 205(1):152–161. doi:10.​1093/​infdis/​jir621 PubMed
188.
189.
Gazzinelli RT, Eltoum I, Wynn TA, Sher A (1993) Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol 151(7):3672–3681PubMed
190.
Bennouna S, Bliss SK, Curiel TJ, Denkers EY (2003) Cross-talk in the innate immune system: neutrophils instruct recruitment and activation of dendritic cells during microbial infection. J Immunol 171(11):6052–6058PubMed
191.
Li ZY, Manthey CL, Perera PY, Sher A, Vogel SN (1994) Toxoplasma gondii soluble antigen induces a subset of lipopolysaccharide-inducible genes and tyrosine phosphoproteins in peritoneal macrophages. Infect Immun 62(8):3434–3440PubMed
192.
Schluter D, Meyer T, Strack A, Reiter S, Kretschmar M, Wiestler OD, Hof H, Deckert M (2001) Regulation of microglia by CD4+ and CD8+ T cells: selective analysis in CD45-congenic normal and Toxoplasma gondii-infected bone marrow chimeras. Brain Pathol 11(1):44–55PubMed
193.
Schluter D, Kaefer N, Hof H, Wiestler OD, Deckert-Schluter M (1997) Expression pattern and cellular origin of cytokines in the normal and Toxoplasma gondii-infected murine brain. Am J Pathol 150(3):1021–1035PubMed
194.
Chang HR, Grau GE, Pechere JC (1990) Role of TNF and IL-1 in infections with Toxoplasma gondii. Immunology 69(1):33–37PubMed
195.
Yap GS, Sher A (1999) Effector cells of both nonhemopoietic and hemopoietic origin are required for interferon (IFN)-gamma- and tumor necrosis factor (TNF)-alpha-dependent host resistance to the intracellular pathogen, Toxoplasma gondii. J Exp Med 189(7):1083–1092PubMed
196.
Zhao Y, Wilson D, Matthews S, Yap GS (2007) Rapid elimination of Toxoplasma gondii by gamma interferon-primed mouse macrophages is independent of CD40 signaling. Infect Immun 75(10):4799–4803. doi:10.​1128/​IAI.​00738-07 PubMed
197.
198.
Subauste CS, Wessendarp M, Sorensen RU, Leiva LE (1999) CD40-CD40 ligand interaction is central to cell-mediated immunity against Toxoplasma gondii: patients with hyper IgM syndrome have a defective type 1 immune response that can be restored by soluble CD40 ligand trimer. J Immunol 162(11):6690–6700PubMed
199.
De Togni P, Goellner J, Ruddle NH, Streeter PR, Fick A, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J et al (1994) Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264(5159):703–707PubMed
200.
Liesenfeld O, Kosek J, Remington JS, Suzuki Y (1996) Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii. J Exp Med 184(2):597–607PubMed
201.
Egan CE, Cohen SB, Denkers EY (2011) Insights into inflammatory bowel disease using Toxoplasma gondii as an infectious trigger. Immunol Cell Biol. doi:10.​1038/​icb.​2011.​93
202.
203.
Egan CE, Craven MD, Leng J, Mack M, Simpson KW, Denkers EY (2009) CCR2-dependent intraepithelial lymphocytes mediate inflammatory gut pathology during Toxoplasma gondii infection. Mucosal Immunol 2(6):527–535. doi:10.​1038/​mi.​2009.​105 PubMed
204.
Egan CE, Maurer KJ, Cohen SB, Mack M, Simpson KW, Denkers EY (2011) Synergy between intraepithelial lymphocytes and lamina propria T cells drives intestinal inflammation during infection. Mucosal Immunol 4(6):658–670. doi:10.​1038/​mi.​2011.​31 PubMed
205.
Ronet C, Darche S, Leite de Moraes M, Miyake S, Yamamura T, Louis JA, Kasper LH, Buzoni-Gatel D (2005) NKT cells are critical for the initiation of an inflammatory bowel response against Toxoplasma gondii. J Immunol 175(2):899–908PubMed
206.
Khan IA, Thomas SY, Moretto MM, Lee FS, Islam SA, Combe C, Schwartzman JD, Luster AD (2006) CCR5 is essential for NK cell trafficking and host survival following Toxoplasma gondii infection. PLoS Pathogens 2(6):e49. doi:10.​1371/​journal.​ppat.​0020049 PubMed
207.
Li W, Buzoni-Gatel D, Debbabi H, Hu MS, Mennechet FJD, Durell BG, Noelle RJ, Kasper LH (2002) CD40/CD154 ligation is required for the development of acute ileitis following oral infection with an intracellular pathogen in mice. Gastroenterology 122(3):762–773. doi:10.​1053/​Gast.​2002.​31888 PubMed
208.
Vossenkamper A, Struck D, Alvarado-Esquivel C, Went T, Takeda K, Akira S, Pfeffer K, Alber G, Lochner M, Forster I, Liesenfeld O (2004) Both IL-12 and IL-18 contribute to small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii, but IL-12 is dominant over IL-18 in parasite control. Eur J Immunol 34(11):3197–3207. doi:10.​1002/​eji.​200424993 PubMed
209.
Munoz M, Heimesaat MM, Danker K, Struck D, Lohmann U, Plickert R, Bereswill S, Fischer A, Dunay IR, Wolk K, Loddenkemper C, Krell HW, Libert C, Lund LR, Frey O, Holscher C, Iwakura Y, Ghilardi N, Ouyang W, Kamradt T, Sabat R, Liesenfeld O (2009) Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. J Exp Med 206(13):3047–3059. doi:10.​1084/​jem.​20090900 PubMed
210.
Liesenfeld O, Kang H, Park D, Nguyen TA, Parkhe CV, Watanabe H, Abo T, Sher A, Remington JS, Suzuki Y (1999) TNF-alpha, nitric oxide and IFN-gamma are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii. Parasite Immunol 21(7):365–376PubMed
211.
212.
Nickdel MB, Lyons RE, Roberts F, Brombacher F, Hunter CA, Alexander J, Roberts CW (2004) Intestinal pathology during acute toxoplasmosis is IL-4 dependent and unrelated to parasite burden. Parasite Immunol 26(2):75–82PubMed
213.
214.
Roberts CW, Ferguson DJ, Jebbari H, Satoskar A, Bluethmann H, Alexander J (1996) Different roles for interleukin-4 during the course of Toxoplasma gondii infection. Infect Immun 64(3):897–904PubMed
215.
Heimesaat MM, Bereswill S, Fischer A, Fuchs D, Struck D, Niebergall J, Jahn HK, Dunay IR, Moter A, Gescher DM, Schumann RR, Gobel UB, Liesenfeld O (2006) Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii. J Immunol 177(12):8785–8795PubMed
216.
Heimesaat MM, Fischer A, Jahn HK, Niebergall J, Freudenberg M, Blaut M, Liesenfeld O, Schumann RR, Gobel UB, Bereswill S (2007) Exacerbation of murine ileitis by toll-like receptor 4 mediated sensing of lipopolysaccharide from commensal Escherichia coli. Gut 56(7):941–948. doi:10.​1136/​gut.​2006.​104497 PubMed
217.
Israelski DM, Araujo FG, Conley FK, Suzuki Y, Sharma S, Remington JS (1989) Treatment with anti-L3T4 (CD4) monoclonal antibody reduces the inflammatory response in toxoplasmic encephalitis. J Immunol 142(3):954–958PubMed
218.
Reichmann G, Villegas EN, Craig L, Peach R, Hunter CA (1999) The CD28/B7 interaction is not required for resistance to Toxoplasma gondii in the brain but contributes to the development of immunopathology. J Immunol 163(6):3354–3362PubMed
219.
Vollmer TL, Waldor MK, Steinman L, Conley FK (1987) Depletion of T-4+ lymphocytes with monoclonal antibody reactivates toxoplasmosis in the central nervous system: a model of superinfection in AIDS. J Immunol 138(11):3737–3741PubMed
220.
221.
222.
Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):263–274PubMed
223.
Gazzinelli RT, Oswald IP, James SL, Sher A (1992) IL-10 inhibits parasite killing and nitrogen oxide production by IFN-gamma-activated macrophages. J Immunol 148(6):1792–1796PubMed
224.
Hunter CA, Abrams JS, Beaman MH, Remington JS (1993) Cytokine mRNA in the central nervous system of SCID mice infected with Toxoplasma gondii: importance of T-cell-independent regulation of resistance to T. gondii. Infect Immun 61(10):4038–4044PubMed
225.
Khan IA, Matsuura T, Kasper LH (1995) IL-10 mediates immunosuppression following primary infection with Toxoplasma gondii in mice. Parasite Immunol 17(4):185–195PubMed
226.
Sher A, Gazzinelli RT, Oswald IP, Clerici M, Kullberg M, Pearce EJ, Berzofsky JA, Mosmann TR, James SL, Morse HC 3rd (1992) Role of T-cell derived cytokines in the downregulation of immune responses in parasitic and retroviral infection. Immunol Rev 127:183–204PubMed
227.
Deckert-Schluter M, Buck C, Weiner D, Kaefer N, Rang A, Hof H, Wiestler OD, Schluter D (1997) Interleukin-10 downregulates the intracerebral immune response in chronic Toxoplasma encephalitis. J Neuroimmunol 76(1–2):167–176PubMed
228.
Jankovic D, Kullberg MC, Feng CG, Goldszmid RS, Collazo CM, Wilson M, Wynn TA, Kamanaka M, Flavell RA, Sher A (2007) Conventional T-bet(+)Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J Exp Med 204(2):273–283. doi:10.​1084/​jem.​20062175 PubMed
229.
Neyer LE, Grunig G, Fort M, Remington JS, Rennick D, Hunter CA (1997) Role of interleukin-10 in regulation of T-cell-dependent and T-cell-independent mechanisms of resistance to Toxoplasma gondii. Infect Immun 65(5):1675–1682PubMed
230.
Roers A, Siewe L, Strittmatter E, Deckert M, Schluter D, Stenzel W, Gruber AD, Krieg T, Rajewsky K, Muller W (2004) T cell-specific inactivation of the interleukin 10 gene in mice results in enhanced T cell responses but normal innate responses to lipopolysaccharide or skin irritation. J Exp Med 200(10):1289–1297. doi:10.​1084/​jem.​20041789 PubMed
231.
Watford WT, Moriguchi M, Morinobu A, O'Shea JJ (2003) The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev 14(5):361–368PubMed
232.
Villarino A, Hibbert L, Lieberman L, Wilson E, Mak T, Yoshida H, Kastelein RA, Saris C, Hunter CA (2003) The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection. Immunity 19(5):645–655PubMed
233.
Stumhofer JS, Silver JS, Laurence A, Porrett PM, Harris TH, Turka LA, Ernst M, Saris CJ, O'Shea JJ, Hunter CA (2007) Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol 8(12):1363–1371PubMed
234.
Hirahara K, Ghoreschi K, Yang X, Takahashi H, Laurence A, Vahedi G, Sciume G, Hall AO, Dupont CD, Francisco LM, Chen Q, Tanaka M, Kanno Y, Sun H, Sharpe AH, Hunter CA, O'Shea JJ (2012) Interleukin-27 priming of T cells controls IL-17-production in trans via induction of the ligand PD-L1. Immunity 36(6):1017–1030PubMed
235.
Stumhofer JS, Laurence A, Wilson EH, Huang E, Tato CM, Johnson LM, Villarino AV, Huang Q, Yoshimura A, Sehy D, Saris CJ, O'Shea JJ, Hennighausen L, Ernst M, Hunter CA (2006) Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 7(9):937–945PubMed
236.
Hamano S, Himeno K, Miyazaki Y, Ishii K, Yamanaka A, Takeda A, Zhang M, Hisaeda H, Mak TW, Yoshimura A, Yoshida H (2003) WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production. Immunity 19(5):657–667PubMed
237.
Rosas LE, Satoskar AA, Roth KM, Keiser TL, Barbi J, Hunter C, de Sauvage FJ, Satoskar AR (2006) Interleukin-27R (WSX-1/T-cell cytokine receptor) gene-deficient mice display enhanced resistance to Leishmania donovani infection but develop severe liver immunopathology. Am J Pathol 168(1):158–169. doi:10.​2353/​ajpath.​2006.​050013 PubMed
238.
Artis D, Villarino A, Silverman M, He W, Thornton EM, Mu S, Summer S, Covey TM, Huang E, Yoshida H, Koretzky G, Goldschmidt M, Wu GD, de Sauvage F, Miller HR, Saris CJ, Scott P, Hunter CA (2004) The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity. J Immunol 173(9):5626–5634PubMed
239.
Pearl JE, Khader SA, Solache A, Gilmartin L, Ghilardi N, deSauvage F, Cooper AM (2004) IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice. J Immunol 173(12):7490–7496PubMed
240.
Holscher C, Holscher A, Ruckerl D, Yoshimoto T, Yoshida H, Mak T, Saris C, Ehlers S (2005) The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis. J Immunol 174(6):3534–3544PubMed
241.
Batten M, Li J, Yi S, Kljavin NM, Danilenko DM, Lucas S, Lee J, de Sauvage FJ, Ghilardi N (2006) Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nat Immunol 7(9):929–936. doi:10.​1038/​ni1375 PubMed
242.
Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB, Gery I, Lee YS, Egwuagu CE (2007) TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13(6):711–718. doi:10.​1038/​nm1585 PubMed
243.
Fitzgerald DC, Ciric B, Touil T, Harle H, Grammatikopolou J, Das Sarma J, Gran B, Zhang GX, Rostami A (2007) Suppressive effect of IL-27 on encephalitogenic Th17 cells and the effector phase of experimental autoimmune encephalomyelitis. J Immunol 179(5):3268–3275PubMed
244.
Villarino AV, Artis D, Bezbradica JS, Miller O, Saris CJ, Joyce S, Hunter CA (2008) IL-27R deficiency delays the onset of colitis and protects from helminth-induced pathology in a model of chronic IBD. Int Immunol 20(6):739–752. doi:10.​1093/​intimm/​dxn032 PubMed
245.
Troy AE, Zaph C, Du Y, Taylor BC, Guild KJ, Hunter CA, Saris CJ, Artis D (2009) IL-27 regulates homeostasis of the intestinal CD4+ effector T cell pool and limits intestinal inflammation in a murine model of colitis. J Immunol 183(3):2037–2044. doi:10.​4049/​jimmunol.​0802918 PubMed
246.
247.
Aliberti J, Serhan C, Sher A (2002) Parasite-induced lipoxin A4 is an endogenous regulator of IL-12 production and immunopathology in Toxoplasma gondii infection. J Exp Med 196(9):1253–1262PubMed
248.
249.
250.
Aliberti J, Hieny S, Reise Sousa C, Serhan CN, Sher A (2002) Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity. Nat Immunol 3(1):76–82. doi:10.​1038/​ni745 PubMed
251.
Machado FS, Johndrow JE, Esper L, Dias A, Bafica A, Serhan CN, Aliberti J (2006) Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent. Nat Med 12(3):330–334. doi:10.​1038/​nm1355 PubMed
252.
Sanchez Y, Rosado Jde D, Vega L, Elizondo G, Estrada-Muniz E, Saavedra R, Juarez I, Rodriguez-Sosa M (2010) The unexpected role for the aryl hydrocarbon receptor on susceptibility to experimental toxoplasmosis. J Biomed Biotechnol 2010:505694. doi:10.​1155/​2010/​505694 PubMed
253.
Yarovinsky F, Hieny S, Sher A (2008) Recognition of Toxoplasma gondii by TLR11 prevents parasite-induced immunopathology. J Immunol 181(12):8478–8484PubMed
254.
Furie B, Furie BC (1988) The molecular basis of blood coagulation. Cell 53(4):505–518PubMed
255.
Mullarky IK, Szaba FM, Berggren KN, Kummer LW, Wilhelm LB, Parent MA, Johnson LL, Smiley ST (2006) Tumor necrosis factor alpha and gamma interferon, but not hemorrhage or pathogen burden, dictate levels of protective fibrin deposition during infection. Infect Immun 74(2):1181–1188. doi:10.​1128/​IAI.​74.​2.​1181-1188.​2006 PubMed
256.
Johnson LL, Berggren KN, Szaba FM, Chen W, Smiley ST (2003) Fibrin-mediated protection against infection-stimulated immunopathology. J Exp Med 197(6):801–806. doi:10.​1084/​jem.​20021493 PubMed
257.
258.
259.
260.
Harris TH, Banigan EJ, Christian DA, Konradt C, Tait Wojno ED, Norose K, Wilson EH, John B, Weninger W, Luster AD, Liu AJ, Hunter CA (2012) Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells. Nature. doi:10.​1038/​nature11098
261.
Yap G, Pesin M, Sher A (2000) Cutting edge: IL-12 is required for the maintenance of IFN-gamma production in T cells mediating chronic resistance to the intracellular pathogen, Toxoplasma gondii. J Immunol 165(2):628–631PubMed
262.
Pelloux H, Pernod G, Ricard J, Renversez TC, Ambroise-Thomas P (1994) Interleukin-6 is secreted by human monocytes after stimulation with anti-Toxoplasma gondii sera. J Infect Dis 169(5):1181–1182PubMed
263.
Fischer HG, Nitzgen B, Reichmann G, Hadding U (1997) Cytokine responses induced by Toxoplasma gondii in astrocytes and microglial cells. Eur J Immunol 27(6):1539–1548. doi:10.​1002/​eji.​1830270633 PubMed
264.
Chou DB, Sworder B, Bouladoux N, Roy CN, Uchida AM, Grigg M, Robey PG, Belkaid Y (2012) Stromal-derived IL-6 alters the balance of myeloerythroid progenitors during Toxoplasma gondii infection. J Leukoc Biol. doi:10.​1189/​jlb.​1011527
265.
Nagineni CN, Detrick B, Hooks JJ (2000) Toxoplasma gondii infection induces gene expression and secretion of interleukin 1 (IL-1), IL-6, granulocyte-macrophage colony-stimulating factor, and intercellular adhesion molecule 1 by human retinal pigment epithelial cells. Infect Immun 68(1):407–410PubMed
266.
Jebbari H, Roberts CW, Ferguson DJ, Bluethmann H, Alexander J (1998) A protective role for IL-6 during early infection with Toxoplasma gondii. Parasite Immunol 20(5):231–239PubMed
267.
Suzuki Y, Rani S, Liesenfeld O, Kojima T, Lim S, Nguyen TA, Dalrymple SA, Murray R, Remington JS (1997) Impaired resistance to the development of toxoplasmic encephalitis in interleukin-6-deficient mice. Infect Immun 65(6):2339–2345PubMed
268.
Browning J, Sizing I, Lawton P, Bourdon P, Rennert P, Majeau G, Ambrose C, Hession C, Miatkowski K, Griffiths D, Ngam-ek A, Meier W, Benjamin C, Hochman P (1997) Characterization of lymphotoxin-alpha beta complexes on the surface of mouse lymphocytes. J Immunol 159(7):3288–3298PubMed
269.
Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Gilbert J, Hibbert L, Churakova T, Travis M, Vaisberg E, Blumenschein WM, Mattson JD, Wagner JL, To W, Zurawski S, McClanahan TK, Gorman DM, Bazan JF, de Waal MR, Rennick D, Kastelein RA (2002) IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity 16(6):779–790PubMed
270.
271.
Pepper M, Dzierszinski F, Wilson E, Tait E, Fang Q, Yarovinsky F, Laufer TM, Roos D, Hunter CA (2008) Plasmacytoid dendritic cells are activated by Toxoplasma gondii to present antigen and produce cytokines. J Immunol 180(9):6229–6236
Metadata
Title
Immune response and immunopathology during toxoplasmosis
Authors
Christopher D. Dupont
David A. Christian
Christopher A. Hunter
Publication date
01-11-2012
Publisher
Springer-Verlag
Published in
Seminars in Immunopathology / Issue 6/2012
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-012-0339-3

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