Skip to main content

Advertisement

SpringerLink
Log in

IL-33/ST2 involves the immunopathology of ocular toxoplasmosis in murine model

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Ocular toxoplasmosis (OT) is the major cause of infective uveitis. Since the eye is a special organ protected by immune privilege, its immune response is different from general organs with Toxoplasma gondii infection. Here, we used Kunming outbred mice to establish OT by intravitreal injection of T. gondii RH strain tachyzoites, IL-33 expression in the eyes was localized by immunostaining, the levels of interleukin (IL)-33 and ST2 (IL-33 receptor) and T-helper (Th)1 and Th2-associated cytokines in the eye and cervical lymph nodes (CLNs) of infected mice were measured, and their correlations were analyzed. Our results showed that the pathologies of the eye and CLN tissues and the IL-33 positive cells in the eye tissues of ocular T. gondii-infected mice were all increased at days 2, 6, and 9 postinfection (p.i.), accompanied with significantly increased transcript levels of IL-33, ST2, IL-1β, IFN-γ, IL-12p40, IL-10, and IL-13 in both the eyes and CLNs, and increased IL-4 expressions in the eyes of T. gondii-infected mice. There were significant correlations between the levels of IFN-γ and ST2, IL-4 and ST2, and IL-13 and ST2 in the eye tissues (P < 0.001), significant correlations between the levels of IFN-γ and ST2 (P < 0.001) as well as between IL-13 and ST2 (P < 0.05) in the CLNs, and significant correlations between the levels of IL-1β and IL-33 in the eyes (P < 0.05) and between IL-1β and IL-33/ST2 in the CLNs (P < 0.001 and P < 0.01, respectively). Our data indicated that IL-33/ST2 may involve the regulation of ocular immunopathology induced by T. gondii infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Barbour M, Allan D, Xu H, Pei C, Chen M, Niedbala W, Fukada SY, Besnard AG, Alves-Filho JC, Tong X, Forrester JV, Liew FY, Jiang HR (2014) IL-33 attenuates the development of experimental autoimmune uveitis. IL-33 attenuates the development of experimental autoimmune uveitis. Eur J Immunol 44(11):3320–3329

    Article  CAS  PubMed  Google Scholar 

  • Charles E, Callegan MC, Blader IJ (2007) The SAG1 Toxoplasma gondii surface protein is not required for acute ocular toxoplasmosis in mice. 75(4):2079–2083

  • da Luz FA, Oliveira AP, Borges D, Brígido PC, Silva MJ (2014) The physiopathological role of IL-33: new highlights in bone biology and a proposed role in periodontal disease. Mediators Inflamm 2014:342410

    PubMed  Google Scholar 

  • Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550

    Article  CAS  PubMed  Google Scholar 

  • Garlanda C, Dinarello CA, Mantovani A (2013) The interleukin-1 family: back to the future. Immunity 39(6):1003–1018

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hayashi S, Chan CC, Gazzinelli RT, Pham NT, Cheung MK, Roberge FG (1996) Protective role of nitric oxide in ocular toxoplasmosis. Br J Ophthalmol 80(7):644–648

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hazlett LD, McClellan SA, Barrett RP, Huang X, Zhang Y, Wu M, van Rooijen N, Szliter E (2010) IL-33 shifts macrophage polarization, promoting resistance against Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci 51(3):1524–1532

    Article  PubMed Central  PubMed  Google Scholar 

  • Holland GN (2003) Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of disease. Am J Ophthalmol 136(6):973–988

    Article  PubMed  Google Scholar 

  • Holland GN (2004) Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. Am J Ophthalmol 137(1):1–17

    PubMed  Google Scholar 

  • 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):4347–4354

    CAS  PubMed  Google Scholar 

  • Jash A, Kwon HK, Sahoo A, Lee CG, So JS, Kim J, Oh YK, Kim YB, Im SH (2010) Topical application of porcine placenta extract inhibits the progression of experimental contact hypersensitivity. J Ethnopharmacol 133(2):654–662

    Article  PubMed  Google Scholar 

  • Jones LA, Alexander J, Roberts CW (2006) Ocular toxoplasmosis: in the storm of the eye. Parasite Immunol 28(12):635–642

    Article  CAS  PubMed  Google Scholar 

  • Jones LA, Roberts F, Nickdel MB, Brombacher F, McKenzie AN, Henriquez FL, Alexander J, Roberts CW (2010) IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii. Eur J Immunol 40(2):426–436

    Article  CAS  PubMed  Google Scholar 

  • Lee YH, Channon JY, Matsuura T, Schwartzman JD, Shin DW, Kasper LH (1999) Functional and quantitative analysis of splenic T cell immune responses following oral toxoplasma gondii infection in mice. Exp Parasitol 91(3):212–221

    Article  CAS  PubMed  Google Scholar 

  • Liew FY, Pitman NI, McInnes IB (2010) Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 10(2):103–110

    Article  CAS  PubMed  Google Scholar 

  • Lin J, Zhang L, Zhao G, Su Z, Deng R, Pflugfelder SC, Li DQ (2013) A novel interleukin 33/ST2 signaling regulates inflammatory response in human corneal epithelium. PLoS One 8(4):e60963

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lu F, Huang S, Kasper LH (2003) Interleukin-10 and pathogenesis of murine ocular toxoplasmosis. Infect Immun 71(12):7159–7163

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Maenz M, Schlüter D, Liesenfeld O, Schares G, Gross U, Pleyer U (2014) Ocular toxoplasmosis past, present and new aspects of an old disease. Prog Retin Eye Res 39:77–106

    Article  CAS  PubMed  Google Scholar 

  • Matsuda A, Okayama Y, Terai N, Yokoi N, Ebihara N, Tanioka H, Kawasaki S, Inatomi T, Katoh N, Ueda E, Hamuro J, Murakami A, Kinoshita S (2009) The role of interleukin-33 in chronic allergic conjunctivitis. Invest Ophthalmol Vis Sci 50(10):4646–4652

    Article  PubMed  Google Scholar 

  • Milovanovic M, Volarevic V, Radosavljevic G, Jovanovic I, Pejnovic N, Arsenijevic N, Lukic ML (2012) IL-33/ST2 axis in inflammation and immunopathology. Immunol Res 52(1–2):89–99

    Article  CAS  PubMed  Google Scholar 

  • Niederkorn JY (2006) See no evil, hear no evil, do no evil: the lessons of immune privilege. Nat Immunol 7(4):354–359

    Article  CAS  PubMed  Google Scholar 

  • Rodríguez-Cerdeira C, Lopez-Bárcenas A, Sánchez-Blanco B, Arenas R (2014) The role of IL-33 in host response to Candida albicans. Sci World J 2014:340690

    Article  Google Scholar 

  • Rostan O, Gangneux JP, Piquet-Pellorce C, Manuel C, McKenzie AN, Guiguen C, Samson M, Robert-Gangneux F (2013) The IL-33/ST2 axis is associated with human visceral leishmaniasis and suppresses Th1 responses in the livers of BALB/c mice infected with Leishmania donovani. MBio 4(5):e00383-13

    Article  PubMed Central  PubMed  Google Scholar 

  • Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type2-associated cytokines. Immunity 23(5):479–490

    Article  CAS  PubMed  Google Scholar 

  • Streilein JW, Ohta K, Mo JS, Taylor AW (2002) Ocular immune privilege and the impact of intraocular inflammation. DNA Cell Biol 21(5–6):453–459

    Article  CAS  PubMed  Google Scholar 

  • Suzuki Y, Yang Q, Yang S, Nguyen N, Lim S, Liesenfeld O, Kojima T, Remington JS (1996) IL-4 is protective against development of toxoplasmic encephalitis. J Immunol 157(6):2564–2569

    CAS  PubMed  Google Scholar 

  • Suzuki Y, Sher A, Yap G, Park D, Neyer LE, Liesenfeld O, Fort M, Kang H, Gufwoli E (2000) IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with Toxoplasma gondii. J Immunol 164(10):5375–5382

    Article  CAS  PubMed  Google Scholar 

  • Torres-Morales E, Taborda L, Cardona N, De-la-Torre A, Sepulveda-Arias JC, Patarroyo MA, Gomez-Marin JE (2014) Th1 and Th2 immune response to P30 and ROP18 peptides in human toxoplasmosis. Med Microbiol Immunol 203(5):315–322

    Article  CAS  PubMed  Google Scholar 

  • Villeret B, Brault L, Couturier-Maillard A, Robinet P, Vasseur V, Secher T, Dimier-Poisson I, Jacobs M, Zheng SG, Quesniaux VF, Ryffel B (2013) Blockade of IL-1R signaling diminishes Paneth cell depletion and Toxoplasma gondii induced ileitis in mice. Am J Clin Exp Immunol 2(1):107–116

    PubMed Central  PubMed  Google Scholar 

  • Yang Q, Li G, Zhu Y, Liu L, Chen E, Turnquist H, Zhang X, Finn OJ, Chen X, Lu B (2011) IL-33 synergizes with TCR and IL-12 signaling to promote the effector function of CD8+ T cells. Eur J Immunol 41(11):3351–3360

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zaiss MM, Maslowski KM, Mosconi I, Guenat N, Marsland BJ, Harris NL (2013) IL-1β suppresses innate IL-25 and IL-33 production and maintains helminth chronicity. PLoS Pathog 9(8):e1003531

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao Q, Chen G (2014) Role of IL-33 and its receptor in T cell-mediated autoimmune diseases. Biomed Res Int 2014:587376

    PubMed Central  PubMed  Google Scholar 

  • Zhao WH, Hu ZQ (2012) Up-regulation of IL-33 expression in various types of murine cells by IL-3 and IL-4. Cytokine 58(2):267–273

    Article  CAS  PubMed  Google Scholar 

  • Zheng Q, Ren Y, Reinach PS, She Y, Xiao B, Hua S, Qu J, Chen W (2014) Reactive oxygen species activated NLRP3 inflammasomes prime environment-induced murine dry eye. Exp Eye Res 125C:1–8

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported in part by grants from the Natural Science Foundation of China to F.L. (nos. 81271854 and 81471973) and the Guangdong Natural Science Foundation, China to F.L. (no. S2013010016736).

Author information

Authors and Affiliations

  1. Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, Guangdong, China

    Xinxin Tong & Fangli Lu

Authors
  1. Xinxin Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fangli Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fangli Lu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tong, X., Lu, F. IL-33/ST2 involves the immunopathology of ocular toxoplasmosis in murine model. Parasitol Res 114, 1897–1905 (2015). https://doi.org/10.1007/s00436-015-4377-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-015-4377-3

Keywords

Search

Navigation