We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Current understanding of Pneumocystis immunology

    Michelle N Kelly

    Section of Pulmonary/Critical Care Medicine, LSU Health Sciences Center, Medical Education Building 3205, 1901 Perdido Street, New Orleans, LA 70112, USA.

    &
    Judd E Shellito

    † Author for correspondence

    Section of Pulmonary/Critical Care Medicine, LSU Health Sciences Center, Medical Education Building 3205, 1901 Perdido Street, New Orleans, LA 70112, USA.

    Published Online:https://doi.org/10.2217/fmb.09.116

    Pneumocystis jirovecii is the opportunistic fungal organism that causes Pneumocystis pneumonia (PCP) in humans. Similar to other opportunistic pathogens, Pneumocystis causes disease in individuals who are immunocompromised, particularly those infected with HIV. PCP remains the most common opportunistic infection in patients with AIDS. Incidence has decreased greatly with the advent of HAART. However, an increase in the non-HIV immunocompromised population, noncompliance with current treatments, emergence of drug-resistant strains and rise in HIV+ cases in developing countries makes Pneumocystis a pathogen of continued interest and a public health threat. A great deal of research interest has addressed therapeutic interventions to boost waning immunity in the host to prevent or treat PCP. This article focuses on research conducted during the previous 5 years regarding the host immune response to Pneumocystis, including innate, cell-mediated and humoral immunity, and associated immunotherapies tested against PCP.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

    Bibliography

    • Gigliotti F, Haidaris P, Haidaris C, Wright T, Van Der Meid K: Further evidence of host species-specific variation in antigens of Pneumocystis carinii using the polymerase chain reaction. J. Infect. Dis.168,191–194 (1993).
    • Pop SM, Kolls JK, Steele C: Pneumocystis: immune recognition and evasion. Int. J. Biochem. Cell Biol.38(1),17–22 (2006).
    • Stringer JR, Beard CB, Miller RF, Wakefield AE: A new name (Pneumocystis jiroveci) for Pneumocystis from humans. Emerg. Infect. Dis.8(9),891–896 (2002).
    • Redhead SA, Cushion MT, Frenkel JK, Stringer JR: Pneumocystis and Trypanosoma cruzi: nomenclature and typifications. J. Eukaryot. Microbiol.53(1),2–11 (2006).
    • Wakefield AE: Detection of DNA sequences identical to Pneumocystis carinii in samples of ambient air. J. Eukaryot. Microbiol.41(5),116S (1994).
    • Wakefield A: DNA sequences identical to Pneumocystis cairnii f. sp. carinii and Pneumocystis carinii f. sp. hominis in samples of air spora. J. Clin. Microbiol.34,1754–1759 (1996).
    • Cushion MT, Collins MS, Linke MJ: Biofilm formation by Pneumocystis spp. Eukaryot. Cell8(2),197–206 (2009).▪▪ Demonstrates ability to passage infectious Pneumocystis in cell-free culture medium.
    • De Souza W, Benchimol M: Basic biology of Pneumocystis carinii: a mini review. Mem. Inst. Oswaldo Cruz100(8),903–908 (2005).
    • Wyder MA, Rasch EM, Kaneshiro ES: Quantitation of absolute Pneumocystis carinii nuclear DNA content. Trophic and cystic forms isolated from infected rat lungs are haploid organisms. J. Eukaryot. Microbiol.45(3),233–239 (1998).
    • 10  Cushion M, Ruffolo J, Walzer P: Analysis of the developmental stages of Pneumocystis cariniiin vitro. Lab. Invest.58,324–331 (1988).
    • 11  Matsumoto Y, Matsuda S, Tegoshi T: Yeast glucan in the cyst wall of Pneumocystis carinii.J. Protozool.36(1),21S–22S (1989).
    • 12  Smulian AG, Sesterhenn T, Tanaka R, Cushion MT: The ste3 pheromone receptor gene of Pneumocystis carinii is surrounded by a cluster of signal transduction genes. Genetics157(3),991–1002 (2001).
    • 13  Vohra PK, Puri V, Kottom Tj, Limper AH, Thomas CF: Pneumocystis carinii ste11, an Hmg-box protein, is phosphorylated by the mitogen activated protein kinase Pcm. Gene312,173–179 (2003).
    • 14  Shepp DH, Hackman RC, Conley FK, Anderson JB, Meyers JD: Toxoplasma gondii reactivation identified by detection of parasitemia in tissue culture. Ann. Intern. Med.103(2),218–221 (1985).
    • 15  Keely SP, Stringer JR, Baughman RP, Linke MJ, Walzer PD, Smulian AG: Genetic variation among Pneumocystis carinii hominis isolates in recurrent pneumocystosis. J. Infect. Dis.172(2),595–598 (1995).
    • 16  Helweg-Larsen J: Pneumocystis jiroveci. Applied molecular microbiology, epidemiology and diagnosis. Dan. Med. Bull.51(3),251–273 (2004).
    • 17  Vargas Sl, Hughes WT, Santolaya ME et al.: Search for primary infection by Pneumocystis carinii in a cohort of normal, healthy infants. Clin. Infect. Dis.32(6),855–861 (2001).
    • 18  Morgan DJ, Vargas Sl, Reyes-Mugica M, Walterspiel JN, Carver W, Gigliotti F: Identification of Pneumocystis carinii in the lungs of infants dying of sudden infant death syndrome. Pediatr. Infect. Dis. J.20(3),306–309 (2001).
    • 19  Lundgren B, Elvin K, Rothman LP, Ljungstrom I, Lidman C, Lundgren JD: Transmission of Pneumocystis carinii from patients to hospital staff. Thorax52(5),422–424 (1997).
    • 20  Miller RF, Ambrose HE, Wakefield AE: Pneumocystis carinii f. sp. hominis DNA in immunocompetent health care workers in contact with patients with P. carinii pneumonia. J. Clin. Microbiol.39(11),3877–3882 (2001).
    • 21  Vargas SL, Ponce CA, Gigliotti F et al.: Transmission of Pneumocystis carinii DNA from a patient with P. carinii pneumonia to immunocompetent contact health care workers. J. Clin. Microbiol.38(4),1536–1538 (2000).
    • 22  Hughes W: Natural mode of acquisition for de novo infection with Pneumocystis carinii. J. Infect. Dis.145,842–848 (1982).
    • 23  Nevez G, Raccurt C, Vincent P, Jounieaux V, Dei-Cas E: Pulmonary colonization with Pneumocystis carinii in human immunodeficiency virus-negative patients: assessing risk with blood CD4+ T cell counts. Clin. Infect. Dis.29(5),1331–1332 (1999).
    • 24  Leigh TR, Kangro HO, Gazzard BG, Jeffries DJ, Collins Jv: DNA amplification by the polymerase chain reaction to detect sub-clinical Pneumocystis carinii colonization in HIV-positive and HIV-negative male homosexuals with and without respiratory symptoms. Respir. Med.87(7),525–529 (1993).
    • 25  Huang L, Crothers K, Morris A et al.: Pneumocystis colonization in HIV-infected patients. J. Eukaryot. Microbiol.50(Suppl.),616–617 (2003).
    • 26  Morris A, Wei K, Afshar K, Huang L: Epidemiology and clinical significance of Pneumocystis colonization. J. Infect. Dis.197(1),10–17 (2008).
    • 27  Davis JL, Welsh DA, Beard CB et al.: Pneumocystis colonisation is common among hospitalised HIV infected patients with non-Pneumocystis pneumonia. Thorax63(4),329–334 (2008).
    • 28  Nevez G, Delbecq S, Raccurt C: Pneumocystis carinii trophozoites in the lungs of patients without pneumocystosis. J. Eukaryot. Microbiol.46(5),109S-110S (1999).
    • 29  Calderon EJ, Regordan C, Medrano FJ, Ollero M, Varela JM: Pneumocystis carinii infection in patients with chronic bronchial disease. Lancet347(9006),977 (1996).
    • 30  Morris A, Sciurba FC, Lebedeva IP et al.: Association of chronic obstructive pulmonary disease severity and Pneumocystis colonization. Am. J. Respir. Crit. Care Med.170(4),408–413 (2004).
    • 31  Norris KA, Morris A, Patil S, Fernandes E: Pneumocystis colonization, airway inflammation, and pulmonary function decline in acquired immunodeficiency syndrome. Immunol. Res.36(1–3),175–187 (2006).▪ Discusses association and colonization of Pneumocystis.
    • 32  Kling HM, Shipley TW, Patil S, Morris A, Norris KA: Pneumocystis colonization in immunocompetent and simian immunodeficiency virus-infected cynomolgus macaques. J. Infect. Dis.199(1),89–96 (2009).
    • 33  Krajicek BJ, Limper AH, Thomas CF Jr: Advances in the biology, pathogenesis and identification of Pneumocystis pneumonia. Curr. Opin. Pulm. Med.14(3),228–234 (2008).
    • 34  Grimwade K, Swingler G: Cotrimoxazole prophylaxis for opportunistic infections in children with HIV infection. Cochrane Database Syst. Rev.2,CD003508 (2003).
    • 35  Kaplan JE, Hanson D, Dworkin MS et al.: Epidemiology of human immunodeficiency virus-associated opportunistic infections in the united states in the era of highly active antiretroviral therapy. Clin. Infect. Dis.30(Suppl. 1),S5–S14 (2000).
    • 36  Morris A, Lundgren JD, Masur H et al.: Current epidemiology of Pneumocystis pneumonia. Emerg. Infect. Dis.10(10),1713–1720 (2004).
    • 37  Cushion MT: Pneumocystis: unraveling the cloak of obscurity. Trends Microbiol.12(5),243–249 (2004).
    • 38  Morris A, Wachter RM, Luce J, Turner J, Huang L: Improved survival with highly active antiretroviral therapy in HIV-infected patients with severe Pneumocystis carinii pneumonia. AIDS17(1),73–80 (2003).
    • 39  Jain MK, Skiest DJ, Cloud JW, Jain Cl, Burns D, Berggren RE: Changes in mortality related to human immunodeficiency virus infection: comparative analysis of inpatient deaths in 1995 and in 1999–2000. Clin. Infect. Dis.36(8),1030–1038 (2003).
    • 40  Walzer PD, Evans HE, Copas AJ, Edwards SG, Grant AD, Miller RF: Early predictors of mortality from Pneumocystis jirovecii pneumonia in HIV-infected patients: 1985–2006. Clin. Infect. Dis.46(4),625–633 (2008).
    • 41  Morris A: Is there anything new in Pneumocystis jirovecii pneumonia? Changes in P. jirovecii pneumonia over the course of the AIDS epidemic. Clin. Infect. Dis.46(4),634–636 (2008).
    • 42  Sowden E, Carmichael AJ: Autoimmune inflammatory disorders, systemic corticosteroids and Pneumocystis pneumonia: a strategy for prevention. BMC Infect. Dis.4,42 (2004).
    • 43  De Castro N, Pavie J, Lagrange-Xelot M, Molina JM: Pneumocystis jiroveci pneumonia in patients with cancer: is it unavoidable? Rev. Mal. Respir.24(6),741–750 (2007).
    • 44  Mansharamani NG, Garland R, Delaney D, Koziel H: Management and outcome patterns for adult Pneumocystis carinii pneumonia, 1985 to 1995: comparison of HIV-associated cases to other immunocompromised states. Chest118(3),704–711 (2000).▪ Explains changing trends in epidemiology of Pneumocystis pneumonia (PCP).
    • 45  Thomas CF Jr, Limper AH: Current insights into the biology and pathogenesis of Pneumocystis pneumonia. Nat. Rev. Microbiol.5(4),298–308 (2007).
    • 46  Patel R, Paya CV: Infections in solid-organ transplant recipients. Clin. Microbiol. Rev.10(1),86–124 (1997).
    • 47  Rodriguez M, Fishman JA: Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients. Clin. Microbiol. Rev.17(4),770–782 (2004).
    • 48  Mikaelsson L, Jacobsson G, Andersson R: Pneumocystis pneumonia – a retrospective study 1991–2001 in Gothenburg, Sweden. J. Infect.53(4),260–265 (2006).▪▪ Retrospective study of PCP cases demonstrating those at risk are not being identified.
    • 49  Sepkowitz KA: Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome. Clin. Infect. Dis.34(8),1098–1107 (2002).
    • 50  Singer NG, Mccune WJ: Prevention of infectious complications in rheumatic disease patients: immunization, Pneumocystis carinii prophylaxis, and screening for latent infections. Curr. Opin. Rheumatol.11(3),173–178 (1999).
    • 51  Li L, Sad S, Kagi D, Mosmann Tr: CD8Tc1 and Tc2 cells secrete distinct cytokine patterns in vitro and in vivo but induce similar inflammatory reactions. J. Immunol.158(9),4152–4161 (1997).
    • 52  Ellerin T, Rubin RH, Weinblatt ME: Infections and anti-tumor necrosis factor a therapy. Arthritis Rheum.48(11),3013–3022 (2003).
    • 53  Yukiko K, Masayoshi H, Ryuji K et al.: Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: a retrospective review and case–control study of 21 patients. Arthritis Care Res.61(3),305–312 (2009).
    • 54  Stratakos G, Kalomenidis I, Papas V et al.: Cough and fever in a female with Crohn’s disease receiving infliximab. Eur. Respir. J.26(2),354–357 (2005).
    • 55  Nahimana A, Rabodonirina M, Bille J, Francioli P, Hauser Pm: Mutations of Pneumocystis jirovecii dihydrofolate reductase associated with failure of prophylaxis. Antimicrob. Agents Chemother.48(11),4301–4305 (2004).
    • 56  Kessl JJ, Hill P, Lange BB, Meshnick SR, Meunier B, Trumpower BL: Molecular basis for atovaquone resistance in Pneumocystis jirovecii modeled in the cytochrome bc(1) complex of Saccharomyces cerevisiae. J. Biol. Chem.279(4),2817–2824 (2004).
    • 57  Huang L, Crothers K, Atzori C et al.: Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance. Emerg. Infect. Dis.10(10),1721–1728 (2004).
    • 58  Beard CB, Fox MR, Lawrence GG et al.: Genetic differences in Pneumocystis isolates recovered from immunocompetent infants and from adults with AIDS: epidemiological implications. J. Infect. Dis.192(10),1815–1818 (2005).
    • 59  Crothers K, Beard CB, Turner J et al.: Severity and outcome of HIV-associated Pneumocystis pneumonia containing Pneumocystis jirovecii dihydropteroate synthase gene mutations. AIDS19(8),801–805 (2005).
    • 60  Fleury J, Escudier E, Pocholle MJ, Carre C, Bernaudin JF: Cell population obtained by bronchoalveolar lavage in Pneumocystis carinii pneumonitis. Acta Cytol.29(5),721–726 (1985).
    • 61  Young JA, Stone JW, Mcgonigle RJ, Adu D, Michael J: Diagnosing Pneumocystis carinii pneumonia by cytological examination of bronchoalveolar lavage fluid: report of 15 cases. J. Clin. Pathol.39(9),945–949 (1986).
    • 62  Young KR Jr, Rankin JA, Naegel GP, Paul ES, Reynolds HY: Bronchoalveolar lavage cells and proteins in patients with the acquired immunodeficiency syndrome. An immunologic analysis. Ann. Intern. Med.103(4),522–533 (1985).
    • 63  Gigliotti F, Ballou LR, Hughes WW, Mosley BD: Purification and initial characterization of a ferret Pneumocystis carinii surface antigen. J. Infect. Dis.158(4),848–854 (1988).
    • 64  Stringer JR, Keely SP: Genetics of surface antigen expression in Pneumocystis carinii.Infect. Immun.69(2),627–639 (2001).
    • 65  Ezekowitz RA, Williams DJ, Koziel H et al.: Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor. Nature351(6322),155–158 (1991).
    • 66  Koziel H, Eichbaum Q, Kruskal BA et al.: Reduced binding and phagocytosis of Pneumocystis carinii by alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation. J. Clin. Invest.102(7),1332–1344 (1998).▪▪ Shows that the alveolar macrophage mannose receptor is downregulated in HIV+ individuals.
    • 67  Fraser IP, Takahashi K, Koziel H, Fardin B, Harmsen A, Ezekowitz RA: Pneumocystis carinii enhances soluble mannose receptor production by macrophages. Microbes Infect.2(11),1305–1310 (2000).
    • 68  Zhang J, Zhu J, Bu X et al.: Cdc42 and RhoB activation are required for mannose receptor-mediated phagocytosis by human alveolar macrophages. Mol. Biol. Cell16(2),824–834 (2005).
    • 69  Zhang J, Zhu J, Imrich A, Cushion M, Kinane TB, Koziel H: Pneumocystis activates human alveolar macrophage NF-κB signaling through mannose receptors. Infect. Immun.72(6),3147–3160 (2004).
    • 70  Zhang J, Tachado SD, Patel N et al.: Negative regulatory role of mannose receptors on human alveolar macrophage proinflammatory cytokine release in vitro. J. Leukoc. Biol.78(3),665–674 (2005).
    • 71  Swain SD, Lee SJ, Nussenzweig MC, Harmsen AG: Absence of the macrophage mannose receptor in mice does not increase susceptibility to Pneumocystis carinii infection in vivo. Infect. Immun.71(11),6213–6221 (2003).
    • 72  De Stefano JA, Cushion MT, Puvanesarajah V, Walzer PD: Analysis of Pneumocystis carinii cyst wall. II. Sugar composition. J. Protozool.37(5),436–441 (1990).
    • 73  De Stefano JA, Myers JD, Du Pont D, Foy JM, Theus SA, Walzer PD: Cell wall antigens of Pneumocystis carinii trophozoites and cysts: purification and carbohydrate analysis of these glycoproteins. J. Eukaryot. Microbiol.45(3),334–343 (1998).
    • 74  Vassallo R, Standing J, Limper AH: β-glucan from Pneumocystis carinii stimulates TNF-α release from alveolar macrophages. J. Eukaryot. Microbiol.46(5),145S (1999).
    • 75  Lebron F, Vassallo R, Puri V, Limper AH: Pneumocystis carinii cell wall β-glucans initiate macrophage inflammatory responses through NF-κB activation. J. Biol. Chem.278(27),25001–25008 (2003).
    • 76  Vassallo R, Kottom TJ, Standing JE, Limper AH: Vitronectin and fibronectin function as glucan binding proteins augmenting macrophage responses to Pneumocystis carinii. Am. J. Respir. Cell Mol. Biol.25(2),203–211 (2001).
    • 77  Ross GD, Cain JA, Lachmann PJ: Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin as functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b. J. Immunol.134(5),3307–3315 (1985).
    • 78  Brown GD, Gordon S: Immune recognition. A new receptor for β-glucans. Nature413(6851),36–37 (2001).
    • 79  Steele C, Marrero L, Swain S et al.: Alveolar macrophage-mediated killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the dectin-1 β-glucan receptor. J. Exp. Med.198(11),1677–1688 (2003).
    • 80  Saijo S, Fujikado N, Furuta T et al.: Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat. Immunol.8(1),39–46 (2007).
    • 81  Taylor MB, Phillips M, Easmon CS: Opsonophagocytosis of Pneumocystis carinii. J. Med. Microbiol.36(4),223–228 (1992).
    • 82  Rapaka RR, Goetzman ES, Zheng M et al.: Enhanced defense against Pneumocystis carinii mediated by a novel dectin-1 receptor fc fusion protein. J. Immunol.178(6),3702–3712 (2007).
    • 83  Ding K, Shibui A, Wang Y, Takamoto M, Matsuguchi T, Sugane K: Impaired recognition by Toll-like receptor 4 is responsible for exacerbated murine Pneumocystis pneumonia. Microbes Infect.7(2),195–203 (2005).
    • 84  Tachado SD, Zhang J, Zhu J, Patel N, Cushion M, Koziel H: Pneumocystis-mediated IL-8 release by macrophages requires coexpression of mannose receptors and TLR2. J. Leukoc. Biol.81(1),205–211 (2007).
    • 85  Zhang C, Wang SH, Lasbury ME et al.: Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina. Infect. Immun.74(3),1857–1864 (2006).
    • 86  Zhang C, Wang SH, Liao CP et al.: Toll-like receptor 2 knockout reduces lung inflammation during Pneumocystis pneumonia but has no effect on phagocytosis of Pneumocystis organisms by alveolar macrophages. J. Eukaryot. Microbiol.53(Suppl. 1),S132–S133 (2006).
    • 87  Wang SH, Zhang C, Lasbury ME et al.: Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia. Microbes Infect.10(4),334–341 (2008).
    • 88  Hollifield M, Bou Ghanem E, De Villiers WJ, Garvy BA: Scavenger receptor a dampens induction of inflammation in response to the fungal pathogen Pneumocystis carinii. Infect. Immun.75(8),3999–4005 (2007).
    • 89  Rooney SA, Young SL, Mendelson CR: Molecular and cellular processing of lung surfactant. FASEB J.8(12),957–967 (1994).
    • 90  Griese M: Pulmonary surfactant in health and human lung diseases: state of the art. Eur. Respir. J.13(6),1455–1476 (1999).
    • 91  Atochina EN, Beers MF, Scanlon ST, Preston AM, Beck JM: P. Carinii induces selective alterations in component expression and biophysical activity of lung surfactant. Am. J. Physiol. Lung Cell Mol. Physiol.278(3),L599–L609 (2000).
    • 92  Beers MF, Atochina EN, Preston AM, Beck JM: Inhibition of lung surfactant protein B expression during Pneumocystis carinii pneumonia in mice. J. Lab. Clin. Med.133(5),423–433 (1999).
    • 93  Mccormack FX, Gibbons R, Ward SR, Kuzmenko A, Wu H, Deepe Gs Jr: Macrophage-independent fungicidal action of the pulmonary collectins. J. Biol. Chem.278(38),36250–36256 (2003).
    • 94  O’riordan DM, Standing JE, Kwon KY, Chang D, Crouch EC, Limper AH: Surfactant protein D interacts with Pneumocystis carinii and mediates organism adherence to alveolar macrophages. J. Clin. Invest.95(6),2699–2710 (1995).
    • 95  Mccormack FX, Festa AL, Andrews RP, Linke M, Walzer PD: The carbohydrate recognition domain of surfactant protein a mediates binding to the major surface glycoprotein of Pneumocystis carinii. Biochemistry36(26),8092–8099 (1997).
    • 96  Atochina EN, Beck JM, Scanlon ST, Preston AM, Beers MF: Pneumocystis carinii pneumonia alters expression and distribution of lung collectins SP-A and SP-D. J. Lab. Clin. Med.137(6),429–439 (2001).
    • 97  Williams MD, Wright JR, March KL, Martin WJ II: Human surfactant protein a enhances attachment of Pneumocystis carinii to rat alveolar macrophages. Am. J. Respir. Cell Mol. Biol.14(3),232–238 (1996).
    • 98  Koziel H, Phelps DS, Fishman JA, Armstrong MY, Richards FF, Rose RM: Surfactant protein-A reduces binding and phagocytosis of Pneumocystis carinii by human alveolar macrophages in vitro. Am. J. Respir. Cell Mol. Biol.18(6),834–843 (1998).
    • 99  Atochina EN, Beck JM, Preston AM et al.: Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice: attenuation of cytokine responses and reactive oxygen–nitrogen species. Infect. Immun.72(10),6002–6011 (2004).
    • 100  Linke MJ, Ashbaugh AD, Demland JA, Walzer PD: Pneumocystis murina colonization in immunocompetent surfactant protein a deficient mice following environmental exposure. Respir. Res.10,10 (2009).
    • 101  Vuk-Pavlovic Z, Mo EK, Icenhour CR, Standing JE, Fisher JH, Limper AH: Surfactant protein D enhances Pneumocystis infection in immune-suppressed mice. Am. J. Physiol. Lung Cell Mol. Physiol.290(3),L442–L449 (2006).
    • 102  Koziel H, Li X, Armstrong MY, Richards FF, Rose RM: Alveolar macrophages from human immunodeficiency virus-infected persons demonstrate impaired oxidative burst response to Pneumocystis cariniiin vitro. Am. J. Respir. Cell Mol. Biol.23(4),452–459 (2000).
    • 103  Shellito JE, Kolls JK, Olariu R, Beck JM: Nitric oxide and host defense against Pneumocystis carinii infection in a mouse model. J. Infect. Dis.173(2),432–439 (1996).
    • 104  Downing JF, Kachel DL, Pasula R, Martin WJ 2nd: γ interferon stimulates rat alveolar macrophages to kill Pneumocystis carinii by L-arginine- and tumor necrosis factor-dependent mechanisms. Infect. Immun.67(3),1347–1352 (1999).
    • 105  Limper AH, Hoyte JS, Standing JE: The role of alveolar macrophages in Pneumocystis carinii degradation and clearance from the lung. J. Clin. Invest.99(9),2110–2117 (1997).▪▪ Demonstrates the importance of alveolar macrophages during PCP infection through chemical depletion.
    • 106  Lasbury ME, Durant PJ, Bartlett MS, Smith JW, Lee CH: Correlation of organism burden and alveolar macrophage counts during infection with Pneumocystis carinii and recovery. Clin. Diagn. Lab. Immunol.10(2),293–302 (2003).▪▪ Shows a correlation between macrophage counts and organism burden, and alveolar macrophage rebounding with cessation of steroid treatment versus Pneumocystis prophylaxis.
    • 107  Lasbury ME, Durant PJ, Ray CA, Tschang D, Schwendener R, Lee CH: Suppression of alveolar macrophage apoptosis prolongs survival of rats and mice with Pneumocystis pneumonia. J. Immunol.176(11),6443–6453 (2006).
    • 108  Lasbury ME, Merali S, Durant PJ, Tschang D, Ray CA, Lee CH: Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia. J. Biol. Chem.282(15),11009–11020 (2007).
    • 109  Liao CP, Lasbury ME, Wang SH et al.: Pneumocystis mediates overexpression of antizyme inhibitor resulting in increased polyamine levels and apoptosis in alveolar macrophages. J. Biol. Chem.284(12),8174–8184 (2009).▪ Demonstrates that Pneumocystis infection results in apoptosis of alveolar macrophages through increased polyamine levels.
    • 110  Brunet A, Bonni A, Zigmond MJ et al.: Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell96(6),857–868 (1999).
    • 111  Kodama T, Hazeki K, Hazeki O, Okada T, Ui M: Enhancement of chemotactic peptide-induced activation of phosphoinositide 3-kinase by granulocyte-macrophage colony-stimulating factor and its relation to the cytokine-mediated priming of neutrophil superoxide-anion production. Biochem. J.337(Pt 2),201–209 (1999).
    • 112  Kamata N, Kutsuna H, Hato F et al.: Activation of human neutrophils by granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor a: role of phosphatidylinositol 3-kinase. Int. J. Hematol.80(5),421–427 (2004).
    • 113  Lasbury ME, Durant PJ, Liao CP, Lee CH: Effects of decreased calmodulin protein on the survival mechanisms of alveolar macrophages during Pneumocystis pneumonia. Infect. Immun. (2009) (Epub ahead of print).
    • 114  Holt PG, Haining S, Nelson DJ, Sedgwick JD: Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J. Immunol.153(1),256–261 (1994).
    • 115  Romani L: Immunity to fungal infections. Nat. Rev. Immunol.4(1),1–23 (2004).
    • 116  Wilson CB, Lewis DB: Basis and implications of selectively diminished cytokine production in neonatal susceptibility to infection. Rev. Infect. Dis.12(Suppl. 4),S410–S420 (1990).
    • 117  Larsen HH, Von Linstow ML, Lundgren B, Hogh B, Westh H, Lundgren JD: Primary Pneumocystis infection in infants hospitalized with acute respiratory tract infection. Emerg. Infect. Dis.13(1),66–72 (2007).
    • 118  Garvy BA, Qureshi MH: Delayed inflammatory response to Pneumocystis carinii infection in neonatal mice is due to an inadequate lung environment. J. Immunol.165(11),6480–6486 (2000).
    • 119  Qureshi MH, Empey KM, Garvy BA: Modulation of proinflammatory responses to Pneumocystis carinii f. sp. muris in neonatal mice by granulocyte-macrophage colony-stimulating factor and IL-4: role of APCS. J. Immunol.174(1),441–448 (2005).
    • 120  Zheng M, Shellito JE, Marrero L et al.: CD4+ T cell-independent vaccination against Pneumocystis carinii in mice. J. Clin. Invest.108(10),1469–1474 (2001).
    • 121  Kobayashi H, Worgall S, O’connor TP, Crystal RG: Interaction of Pneumocystis carinii with dendritic cells and resulting host responses to P. carinii. J. Immunother.30(1),54–63 (2007).
    • 122  Carmona EM, Vassallo R, Vuk-Pavlovic Z, Standing JE, Kottom TJ, Limper AH: Pneumocystis cell wall β-glucans induce dendritic cell costimulatory molecule expression and inflammatory activation through a fas–fas ligand mechanism. J. Immunol.177(1),459–467 (2006).
    • 123  Rosenzweig SD, Holland SM: Phagocyte immunodeficiencies and their infections. J. Allergy Clin. Immunol.113(4),620–626 (2004).
    • 124  Jensen BN, Lisse IM, Gerstoft J, Borgeskov S, Skinhoj P: Cellular profiles in bronchoalveolar lavage fluid of HIV-infected patients with pulmonary symptoms: relation to diagnosis and prognosis. AIDS5(5),527–533 (1991).
    • 125  Sadaghdar H, Huang ZB, Eden E: Correlation of bronchoalveolar lavage findings to severity of Pneumocystis carinii pneumonia in AIDS. Evidence for the development of high-permeability pulmonary edema. Chest102(1),63–69 (1992).
    • 126  Swain SD, Wright TW, Degel PM, Gigliotti F, Harmsen AG: Neither neutrophils nor reactive oxygen species contribute to tissue damage during Pneumocystis pneumonia in mice. Infect. Immun.72(10),5722–5732 (2004).
    • 127  Pottratz ST, Reese S, Sheldon JL: Pneumocystis carinii induces interleukin 6 production by an alveolar epithelial cell line. Eur J. Clin. Invest.28(5),424–429 (1998).
    • 128  Benfield TL, Lundgren B, Shelhamer JH, Lundgren JD: Pneumocystis carinii major surface glycoprotein induces interleukin-8 and monocyte chemoattractant protein-1 release from a human alveolar epithelial cell line. Eur. J. Clin. Invest.29(8),717–722 (1999).
    • 129  Wang J, Gigliotti F, Bhagwat SP, Maggirwar SB, Wright TW: Pneumocystis stimulates mcp-1 production by alveolar epithelial cells through a JNK-dependent mechanism. Am. J. Physiol. Lung Cell Mol. Physiol.292(6),L1495–L1505 (2007).
    • 130  Hahn PY, Evans SE, Kottom TJ, Standing JE, Pagano RE, Limper AH: Pneumocystis carinii cell wall β-glucan induces release of macrophage inflammatory protein-2 from alveolar epithelial cells via a lactosylceramide-mediated mechanism. J. Biol. Chem.278(3),2043–2050 (2003).
    • 131  Wang J, Gigliotti F, Maggirwar S, Johnston C, Finkelstein JN, Wright TW: Pneumocystis carinii activates the NF-κB signaling pathway in alveolar epithelial cells. Infect. Immun.73(5),2766–2777 (2005).
    • 132  Evans SE, Hahn PY, Mccann F, Kottom TJ, Pavlovic ZV, Limper AH: Pneumocystis cell wall β-glucans stimulate alveolar epithelial cell chemokine generation through nuclear factor-κb-dependent mechanisms. Am. J. Respir. Cell Mol. Biol.32(6),490–497 (2005).
    • 133  Beck JM, Preston AM, Wilcoxen SE, Morris SB, Sturrock A, Paine R 3rd: Critical roles of inflammation and apoptosis in improved survival in a model of hyperoxia-induced acute lung injury in Pneumocystis murina-infected mice. Infect. Immun.77(3),1053–1060 (2009).▪ Demonstrates that lung epithelial cells have increased apoptosis mediated through Fas–Fas ligand interactions during PCP, particularly with the stress of hyperoxia.
    • 134  Phair J, Munoz A, Detels R, Kaslow R, Rinaldo C, Saah A: The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter aids cohort study group. N. Engl. J. Med.322(3),161–165 (1990).
    • 135  Shellito J, Suzara VV, Blumenfeld W, Beck JM, Steger HJ, Ermak TH: A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes. J. Clin. Invest.85(5),1686–1693 (1990).
    • 136  Rose CM, Kimzey SL, Green JM: The host response of CD28-deficient mice to Pneumocystis infection. Microb. Pathog.40(1),23–28 (2006).
    • 137  Beck JM, Blackmon MB, Rose CM, Kimzey SL, Preston AM, Green JM: T cell costimulatory molecule function determines susceptibility to infection with Pneumocystis carinii in mice. J. Immunol.171(4),1969–1977 (2003).
    • 138  Wright TW, Gigliotti F, Finkelstein JN, Mcbride JT, An CL, Harmsen AG: Immune-mediated inflammation directly impairs pulmonary function, contributing to the pathogenesis of Pneumocystis carinii pneumonia. J. Clin. Invest.104(9),1307–1317 (1999).
    • 139  Roths JB, Sidman CL: Both immunity and hyperresponsiveness to Pneumocystis carinii result from transfer of CD4+ but not CD8+ T cells into severe combined immunodeficiency mice. J. Clin. Invest.90(2),673–678 (1992).
    • 140  Wu AK, Cheng VC, Tang BS et al.: The unmasking of Pneumocystis jiroveci pneumonia during reversal of immunosuppression: case reports and literature review. BMC Infect. Dis.4(1),57 (2004).
    • 141  Cheng VC, Yuen KY, Chan WM, Wong SS, Ma ES, Chan RM: Immunorestitution disease involving the innate and adaptive response. Clin. Infect. Dis.30(6),882–892 (2000).
    • 142  Koval CE, Gigliotti F, Nevins D, Demeter LM: Immune reconstitution syndrome after successful treatment of Pneumocystis carinii pneumonia in a man with human immunodeficiency virus type 1 infection. Clin. Infect. Dis.35(4),491–493 (2002).
    • 143  Atochina-Vasserman EN, Gow AJ, Abramova H et al.: Immune reconstitution during Pneumocystis lung infection: disruption of surfactant component expression and function by S-nitrosylation. J. Immunol.182(4),2277–2287 (2009).
    • 144  Bhagwat SP, Gigliotti F, Xu H, Wright TW: Contribution of T cell subsets to the pathophysiology of Pneumocystis-related immunorestitution disease. Am. J. Physiol. Lung Cell Mol. Physiol.291(6),L1256–L1266 (2006).
    • 145  Swain SD, Meissner NN, Harmsen AG: CD8 T cells modulate CD4 T-cell and eosinophil-mediated pulmonary pathology in Pneumocystis pneumonia in B-cell-deficient mice. Am. J. Pathol.168(2),466–475 (2006).▪ Demonstrates the roles of CD4+ and CD8+ T cells during immune reconstitution disease.
    • 146  Hori S, Carvalho TL, Demengeot J: CD25+ CD4+ regulatory T cells suppress CD4+ T cell-mediated pulmonary hyperinflammation driven by Pneumocystis carinii in immunodeficient mice. Eur. J. Immunol.32(5),1282–1291 (2002).
    • 147  Mckinley L, Logar AJ, Mcallister F, Zheng M, Steele C, Kolls JK: Regulatory T cells dampen pulmonary inflammation and lung injury in an animal model of Pneumocystis pneumonia. J. Immunol.177(9),6215–6226 (2006).
    • 148  Gigliotti F, Crow EL, Bhagwat SP, Wright TW: Sensitized CD8+ T cells fail to control organism burden but accelerate the onset of lung injury during Pneumocystis carinii pneumonia. Infect. Immun.74(11),6310–6316 (2006).
    • 149  Meissner NN, Lund FE, Han S, Harmsen A: CD8 T cell-mediated lung damage in response to the extracellular pathogen Pneumocystis is dependent on MHC class I expression by radiation-resistant lung cells. J. Immunol.175(12),8271–8279 (2005).
    • 150  Wright TW, Pryhuber GS, Chess PR, Wang Z, Notter RH, Gigliotti F: TNF receptor signaling contributes to chemokine secretion, inflammation, and respiratory deficits during Pneumocystis pneumonia. J. Immunol.172(4),2511–2521 (2004).
    • 151  Pryhuber GS, Huyck HL, Bhagwat S et al.: Parenchymal cell TNF receptors contribute to inflammatory cell recruitment and respiratory failure in Pneumocystis carinii-induced pneumonia. J. Immunol.181(2),1409–1419 (2008).
    • 152  Kolls JK, Habetz S, Shean MK et al.: IFN-γ and CD8+ T cells restore host defenses against Pneumocystis carinii in mice depleted of CD4+ T cells. J. Immunol.162(5),2890–2894 (1999).▪▪ Shows gene transfer of IFN-γ results in organism clearance mediated by CD8+ T cells in the absence of CD4+ T cells.
    • 153  Mcallister F, Steele C, Zheng M et al.: T cytotoxic-1 CD8+ T cells are effector cells against Pneumocystis in mice. J. Immunol.172(2),1132–1138 (2004).▪▪ Demonstrates the effector activity of T cytotoxic 1 CD8+ T cells verses the pathogenesis of T cytotoxic 2 CD8+ T cells.
    • 154  Mcallister F, Steele C, Zheng M, Shellito JE, Kolls JK: In vitro effector activity of Pneumocystis murina-specific T-cytotoxic-1 CD8+ T cells: role of granulocyte-macrophage colony-stimulating factor. Infect. Immun.73(11),7450–7457 (2005).
    • 155  Mcallister F, Ruan S, Steele C et al.: Cxcr3 and IFN protein-10 in Pneumocystis pneumonia. J. Immunol.177(3),1846–1854 (2006).
    • 156  Chang H, Yeh HC, Su YC, Lee MH: Pneumocystis jiroveci pneumonia in patients with non-Hodgkin’s lymphoma receiving chemotherapy containing rituximab. J. Chin. Med. Assoc.71(11),579–582 (2008).
    • 157  Daly KR, Koch J, Levin L, Walzer PD: Enzyme-linked immunosorbent assay and serologic responses to Pneumocystis jiroveci. Emerg. Infect. Dis.10(5),848–854 (2004).
    • 158  Bishop LR, Kovacs JA: Quantitation of anti-Pneumocystis jiroveci antibodies in healthy persons and immunocompromised patients. J. Infect. Dis.187(12),1844–1848 (2003).
    • 159  Daly K, Koch J, Respaldiza N et al.: Geographical variation in serological responses to recombinant Pneumocystis jirovecii major surface glycoprotein antigens. Clin. Microbiol. Infect.15(10),937–942 (2009).▪ Shows that geographical location plays a role in antibody responses to Pneumocystis antigens.
    • 160  Walzer PD, Djawe K, Levin L et al.: Long-term serologic responses to the Pneumocystis jirovecii major surface glycoprotein in HIV-positive individuals with and without P. jirovecii infection. J. Infect. Dis.199(9),1335–1344 (2009).
    • 161  Furuta T, Fujiwara K, Yamanouchi K, Ueda K: Detection of antibodies to Pneumocystis carinii by enzyme-linked immunosorbent assay in experimentally infected mice. J. Parasitol.71(4),522–523 (1985).
    • 162  Walzer PD, Rutledge ME: Humoral immunity in experimental Pneumocystis carinii infection. I. Serum and bronchial lavage fluid antibody responses in rats. J. Lab. Clin. Med.97(6),820–833 (1981).
    • 163  Gigliotti F, Hughes WT: Passive immunoprophylaxis with specific monoclonal antibody confers partial protection against Pneumocystis carinii pneumonitis in animal models. J. Clin. Invest.81(6),1666–1668 (1988).
    • 164  Gigliotti F, Haidaris CG, Wright TW, Harmsen AG: Passive intranasal monoclonal antibody prophylaxis against murine Pneumocystis carinii pneumonia. Infect. Immun.70(3),1069–1074 (2002).
    • 165  Roths JB, Sidman CL: Single and combined humoral and cell-mediated immunotherapy of Pneumocystis carinii pneumonia in immunodeficient SCID mice. Infect. Immun.61(5),1641–1649 (1993).
    • 166  Wells J, Gigliotti F, Simpson-Haidaris PJ, Haidaris CG: Epitope mapping of a protective monoclonal antibody against Pneumocystis carinii with shared reactivity to streptococcus pneumoniae surface antigen PSPA. Infect. Immun.72(3),1548–1556 (2004).
    • 167  Wells J, Haidaris CG, Wright TW, Gigliotti F: Complement and fc function are required for optimal antibody prophylaxis against Pneumocystis carinii pneumonia. Infect. Immun.74(1),390–393 (2006).
    • 168  Harmsen AG, Chen W, Gigliotti F: Active immunity to Pneumocystis carinii reinfection in T-cell-depleted mice. Infect. Immun.63(7),2391–2395 (1995).
    • 169  Pascale JM, Shaw MM, Durant PJ et al.: Intranasal immunization confers protection against murine Pneumocystis carinii lung infection. Infect. Immun.67(2),805–809 (1999).
    • 170  Garvy BA, Wiley JA, Gigliotti F, Harmsen AG: Protection against Pneumocystis carinii pneumonia by antibodies generated from either T helper 1 or T helper 2 responses. Infect. Immun.65(12),5052–5056 (1997).
    • 171  Wells J, Haidaris CG, Wright TW, Gigliotti F: Active immunization against Pneumocystis carinii with a recombinant P. carinii antigen. Infect. Immun.74(4),2446–2448 (2006).
    • 172  Wiley JA, Harmsen AG: CD40 ligand is required for resolution of Pneumocystis carinii pneumonia in mice. J. Immunol.155(7),3525–3529 (1995).
    • 173  Lund FE, Schuer K, Hollifield M, Randall TD, Garvy BA: Clearance of Pneumocystis carinii in mice is dependent on B cells but not on P. carinii-specific antibody. J. Immunol.171(3),1423–1430 (2003).
    • 174  Lund FE, Hollifield M, Schuer K, Lines JL, Randall TD, Garvy BA: B cells are required for generation of protective effector and memory CD4 cells in response to Pneumocystis lung infection. J. Immunol.176(10),6147–6154 (2006).
    • 175  Zheng M, Ramsay AJ, Robichaux MB et al.: CD4+ T cell-independent DNA vaccination against opportunistic infections. J. Clin. Invest.115(12),3536–3544 (2005).
    • 176  Ishimine T, Kawakami K, Nakamoto A, Saito A: Analysis of cellular response and g interferon synthesis in bronchoalveolar lavage fluid and lung homogenate of mice infected with Pneumocystis carinii. Microbiol. Immunol.39(1),49–58 (1995).
    • 177  Pesanti EL: Interaction of cytokines and alveolar cells with Pneumocystis cariniiin vitro. J. Infect. Dis.163(3),611–616 (1991).
    • 178  Garvy BA, Ezekowitz RA, Harmsen AG: Role of γ interferon in the host immune and inflammatory responses to Pneumocystis carinii infection. Infect. Immun.65(2),373–379 (1997).
    • 179  Garvy BA, Gigliotti F, Harmsen AG: Neutralization of interferon-γ exacerbates Pneumocystis-driven interstitial pneumonitis after bone marrow transplantation in mice. J. Clin. Invest.99(7),1637–1644 (1997).
    • 180  Shear HL, Valladares G, Narachi MA: Enhanced treatment of Pneumocystis carinii pneumonia in rats with interferon-γ and reduced doses of trimethoprim/sulfamethoxazole. J. Acquir. Immune Defic. Syndr.3(10),943–948 (1990).
    • 181  Beck JM, Liggitt HD, Brunette EN, Fuchs HJ, Shellito JE, Debs RJ: Reduction in intensity of Pneumocystis carinii pneumonia in mice by aerosol administration of γ interferon. Infect. Immun.59(11),3859–3862 (1991).
    • 182  Levy JA: The importance of the innate immune system in controlling HIV infection and disease. Trends Immunol.22(6),312–316 (2001).
    • 183  Siegal FP, Fitzgerald-Bocarsly P, Holland BK, Shodell M: Interferon-α generation and immune reconstitution during antiretroviral therapy for human immunodeficiency virus infection. AIDS15(13),1603–1612 (2001).
    • 184  Levy DE, Marie I, Prakash A: Ringing the interferon alarm: differential regulation of gene expression at the interface between innate and adaptive immunity. Curr. Opin. Immunol.15(1),52–58 (2003).
    • 185  Zhang X, Sun S, Hwang I, Tough DF, Sprent J: Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity8(5),591–599 (1998).
    • 186  Meissner N, Rutkowski M, Harmsen AL, Han S, Harmsen AG: Type I interferon signaling and B cells maintain hemopoiesis during Pneumocystis infection of the lung. J. Immunol.178(10),6604–6615 (2007).
    • 187  Meissner NN, Swain S, Tighe M, Harmsen A, Harmsen A: Role of type I IFNs in pulmonary complications of Pneumocystis murina infection. J. Immunol.174(9),5462–5471 (2005).▪ Demonstrates that type I IFN signaling mediates the immune response to Pneumocystis.
    • 188  Tamburrini E, De Luca A, Ventura G et al.: Pneumocystis carinii stimulates in vitro production of tumor necrosis factor-α by human macrophages. Med. Microbiol. Immunol.180(1),15–20 (1991).
    • 189  Kolls JK, Lei D, Vazquez C et al.: Exacerbation of murine Pneumocystis carinii infection by adenoviral-mediated gene transfer of a TNF inhibitor. Am. J. Respir. Cell Mol. Biol.16(2),112–118 (1997).
    • 190  Chen W, Havell EA, Harmsen AG: Importance of endogenous tumor necrosis factor α and γ interferon in host resistance against Pneumocystis carinii infection. Infect. Immun.60(4),1279–1284 (1992).
    • 191  Dinarello CA: Interleukin-1 and its biologically related cytokines. Adv. Immunol.44,153–205 (1989).
    • 192  Roy S, Fitz-Gibbon L, Poulin L, Wainberg MA: Infection of human monocytes/macrophages by HIV-1: effect on secretion of IL-1 activity. Immunology64(2),233–239 (1988).
    • 193  Chen W, Havell EA, Moldawer LL, Mcintyre KW, Chizzonite RA, Harmsen AG: Interleukin 1: an important mediator of host resistance against Pneumocystis carinii. J. Exp. Med.176(3),713–718 (1992).
    • 194  Chen W, Havell EA, Gigliotti F, Harmsen AG: Interleukin-6 production in a murine model of Pneumocystis carinii pneumonia: relation to resistance and inflammatory response. Infect. Immun.61(1),97–102 (1993).
    • 195  Linke M, Ashbaugh A, Koch J, Tanaka R, Walzer P: Efficient resolution of Pneumocystismurina infection in surfactant protein A-deficient mice following withdrawal of corticosteroid-induced immunosuppression. J. Med. Microbiol.55(Pt 2),143–147 (2006).
    • 196  Jones TC: The effect of granulocyte-macrophage colony stimulating factor (RGM-CSF) on macrophage function in microbial disease. Med. Oncol.13(3),141–147 (1996).
    • 197  Mandujano JF, D’Souza NB, Nelson S, Summer WR, Beckerman RC, Shellito JE: Granulocyte-macrophage colony stimulating factor and Pneumocystis carinii pneumonia in mice. Am. J. Respir. Crit. Care Med.151(4),1233–1238 (1995).
    • 198  Paine R 3rd, Preston AM, Wilcoxen S et al.: Granulocyte-macrophage colony-stimulating factor in the innate immune response to Pneumocystis carinii pneumonia in mice. J. Immunol.164(5),2602–2609 (2000).
    • 199  Denis M, Ghadirian E: Dysregulation of interleukin 8, interleukin 10, and interleukin 12 release by alveolar macrophages from HIV type 1-infected subjects. AIDS Res. Hum. Retroviruses10(12),1619–1627 (1994).
    • 200  Ruan S, Mckinley L, Zheng M et al.: Interleukin-12 and host defense against murine Pneumocystis pneumonia. Infect. Immun.76(5),2130–2137 (2008).
    • 201  Moore KW, De Waal Malefyt R, Coffman RL, O’garra A: Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol.19,683–765 (2001).
    • 202  Ruan S, Tate C, Lee JJ, Ritter T, Kolls JK, Shellito JE: Local delivery of the viral interleukin-10 gene suppresses tissue inflammation in murine Pneumocystis carinii infection. Infect. Immun.70(11),6107–6113 (2002).
    • 203  Qureshi MH, Harmsen AG, Garvy BA: IL-10 modulates host responses and lung damage induced by Pneumocystis carinii infection. J. Immunol.170(2),1002–1009 (2003).
    • 204  Dubin PJ, Kolls JK: Th17 cytokines and mucosal immunity. Immunol. Rev.226,160–171 (2008).
    • 205  Zelante T, Bozza S, De Luca A et al.: Th17 cells in the setting of Aspergillus infection and pathology. Med. Mycol.47(Suppl. 1),S162–S169 (2009).
    • 206  Zelante T, De Luca A, D’angelo C, Moretti S, Romani L: IL-17/Th17 in antifungal immunity: what’s new? Eur. J. Immunol.39(3),645–648 (2009).
    • 207  Aggarwal S, Ghilardi N, Xie MH, De Sauvage FJ, Gurney AL: Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J. Biol. Chem.278(3),1910–1914 (2003).
    • 208  Mckenzie BS, Kastelein RA, Cua DJ: Understanding the IL-23–IL-17 immune pathway. Trends Immunol.27(1),17–23 (2006).
    • 209  Rudner XL, Happel KI, Young EA, Shellito JE: Interleukin-23 (IL-23)–IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect. Immun.75(6),3055–3061 (2007).
    • 210  Wright TW, Johnston CJ, Harmsen AG, Finkelstein JE: Chemokine gene expression during Pneumocystis carinii-driven pulmonary inflammation. Infect. Immun.67(7),3452–3460 (1999).
    • 211  Sauty A, Dziejman M, Taha RA et al.: The T cell-specific CXC chemokines IP-10, MIG, and I-TAC are expressed by activated human bronchial epithelial cells. J. Immunol.162(6),3549–3558 (1999).
    • 212  Gasperini S, Marchi M, Calzetti F et al.: Gene expression and production of the monokine induced by IFN-γ (MIG), IFN-inducible T cell α chemoattractant (I-TAC), and IFN-γ-inducible protein-10 (IP-10) chemokines by human neutrophils. J. Immunol.162(8),4928–4937 (1999).
    • 213  Wiley R, Palmer K, Gajewska B et al.: Expression of the Th1 chemokine IFN-γ-inducible protein 10 in the airway alters mucosal allergic sensitization in mice. J. Immunol.166(4),2750–2759 (2001).
    • 214  Agostini C, Facco M, Siviero M et al.: CXC chemokines IP-10 and MIG expression and direct migration of pulmonary CD8+/CXCR3+ T cells in the lungs of patients with HIV infection and T-cell alveolitis. Am. J. Respir. Crit. Care Med.162(4 Pt 1),1466–1473 (2000).
    • 215  Cole AM, Ganz T, Liese AM, Burdick MD, Liu L, Strieter RM: Cutting edge: IFN-inducible ELR-CXC chemokines display defensin-like antimicrobial activity. J. Immunol.167(2),623–627 (2001).
    • 216  Crawford MA, Zhu Y, Green CS et al.: Antimicrobial effects of interferon-inducible CXC chemokines against Bacillus anthracis spores and bacilli. Infect. Immun.77(4),1664–1678 (2009).
    • 217  Mcallister F, Shellito J, Steele C, Kolls JK: Ip-10 effector activity against Pneumocystis carinii. Presented at: American Thoracic Society. San Diego, CA, USA, 20–25 May 2005.