IL-33-Mediated Protection against Experimental Cerebral Malaria Is Linked to Induction of Type 2 Innate Lymphoid Cells, M2 Macrophages and Regulatory T Cells

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Cerebral malaria (CM) caused by the parasite Plasmodium sp. is a fatal disease, especially in children. Currently there is no effective treatment. We report here our investigation on the role of a recently discovered cytokine IL-33, in treating experimental cerebral malaria (ECM) in the susceptible C57BL/6 mice. IL-33 protects the mice against ECM. The protection is accompanied by a reduction of Th1 response and the enhancement of type 2 cytokine response. We also found that IL-33 mediates its protective effect by inducing a population of type 2 innate lymphoid cells (ILC2), which then polarize macrophages to alternatively-activated phenotypes (M2). M2 in turn expand regulatory T cells (Tregs) which suppress the deleterious Th1 response. Our report therefore reveals hitherto unrecognised mechanisms of the regulation of ECM and provide a novel function of IL-33.

Vyšlo v časopise: IL-33-Mediated Protection against Experimental Cerebral Malaria Is Linked to Induction of Type 2 Innate Lymphoid Cells, M2 Macrophages and Regulatory T Cells. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004607
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004607

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Zdroje

1. World Health Organization (2012) World Malaria Report 2012.

2. Belnoue E, Potter SM, Rosa DS, Mauduit M, Gruner AC, et al. (2008) Control of pathogenic CD8+ T cell migration to the brain by IFN-gamma during experimental cerebral malaria. Parasite Immunol 30: 544–553. doi: 10.1111/j.1365-3024.2008.01053.x 18665903

3. Campanella GS, Tager AM, El Khoury JK, Thomas SY, Abrazinski TA, et al. (2008) Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria. Proc Natl Acad Sci U S A 105: 4814–4819. doi: 10.1073/pnas.0801544105 18347328

4. van der Heyde HC, Nolan J, Combes V, Gramaglia I, Grau GE (2006) A unified hypothesis for the genesis of cerebral malaria: sequestration, inflammation and hemostasis leading to microcirculatory dysfunction. Trends Parasitol 22: 503–508. doi: 10.1016/j.pt.2006.09.002 16979941

5. Shikani HJ, Freeman BD, Lisanti MP, Weiss LM, Tanowitz HB, et al. (2012) Cerebral malaria: we have come a long way. Am J Pathol 181: 1484–1492. doi: 10.1016/j.ajpath.2012.08.010 23021981

6. Angulo I, Fresno M (2002) Cytokines in the pathogenesis of and protection against malaria. Clin Diagn Lab Immunol 9: 1145–1152. 12414742

7. Knowles SC (2011) The effect of helminth co-infection on malaria in mice: a meta-analysis. Int J Parasitol 41: 1041–1051. doi: 10.1016/j.ijpara.2011.05.009 21777589

8. de Kossodo S, Grau GE (1993) Profiles of cytokine production in relation with susceptibility to cerebral malaria. J Immunol 151: 4811–4820. 8409439

9. Bagot S, Campino S, Penha-Goncalves C, Pied S, Cazenave PA, et al. (2002) Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain. Proc Natl Acad Sci U S A 99: 9919–9923. doi: 10.1073/pnas.152215199 12114535

10. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, et al. (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23: 479–490. doi: 10.1016/j.immuni.2005.09.015 16286016

11. 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: 103–110. doi: 10.1038/nri2692 20081870

12. Mirchandani AS, Salmond RJ, Liew FY (2012) Interleukin-33 and the function of innate lymphoid cells. Trends Immunol 33: 389–396. doi: 10.1016/j.it.2012.04.005 22609147

13. Liew FY (2012) IL-33: a Janus cytokine. Ann Rheum Dis 71 Suppl 2: i101–104. doi: 10.1136/annrheumdis-2011-200589 22460136

14. Kurowska-Stolarska M, Stolarski B, Kewin P, Murphy G, Corrigan CJ, et al. (2009) IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J Immunol 183: 6469–6477. doi: 10.4049/jimmunol.0901575 19841166

15. Franke-Fayard B, Fonager J, Braks A, Khan SM, Janse CJ (2010) Sequestration and tissue accumulation of human malaria parasites: can we learn anything from rodent models of malaria? PLoS Pathog 6: e1001032. doi: 10.1371/journal.ppat.1001032 20941396

16. Gimenez F, Barraud de Lagerie S, Fernandez C, Pino P, Mazier D (2003) Tumor necrosis factor alpha in the pathogenesis of cerebral malaria. Cell Mol Life Sci 60: 1623–1635. doi: 10.1007/s00018-003-2347-x 14504653

17. Haque A, Best SE, Unosson K, Amante FH, de Labastida F, et al. (2011) Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria. J Immunol 186: 6148–6156. doi: 10.4049/jimmunol.1003955 21525386

18. Salmond RJ, Mirchandani AS, Besnard AG, Bain CC, Thomson NC, et al. (2012) IL-33 induces innate lymphoid cell-mediated airway inflammation by activating mammalian target of rapamycin. J Allergy Clin Immunol 130: 1159–1166 e1156. doi: 10.1016/j.jaci.2012.05.018 22738676

19. Yasuda K, Muto T, Kawagoe T, Matsumoto M, Sasaki Y, et al. (2012) Contribution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode-infected mice. Proc Natl Acad Sci U S A 109: 3451–3456. doi: 10.1073/pnas.1201042109 22331917

20. Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, et al. (2013) Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med 210: 535–549. doi: 10.1084/jem.20121964 23420878

21. Barlow JL, Bellosi A, Hardman CS, Drynan LF, Wong SH, et al. (2012) Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity. J Allergy Clin Immunol 129: 191–198 e191–194. doi: 10.1016/j.jaci.2011.09.041 22079492

22. Barlow JL, Peel S, Fox J, Panova V, Hardman CS, et al. (2013) IL-33 is more potent than IL-25 in provoking IL-13-producing nuocytes (type 2 innate lymphoid cells) and airway contraction. J Allergy Clin Immunol 132: 933–941. doi: 10.1016/j.jaci.2013.05.012 23810766

23. Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5: 953–964. doi: 10.1038/nri1733 16322748

24. Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M (2013) Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol 229: 176–185. doi: 10.1002/path.4133 23096265

25. Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, et al. (2010) Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464: 1367–1370. doi: 10.1038/nature08900 20200518

26. Amante FH, Stanley AC, Randall LM, Zhou Y, Haque A, et al. (2007) A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. Am J Pathol 171: 548–559. doi: 10.2353/ajpath.2007.061033 17600128

27. Vigario AM, Gorgette O, Dujardin HC, Cruz T, Cazenave PA, et al. (2007) Regulatory CD4+ CD25+ Foxp3+ T cells expand during experimental Plasmodium infection but do not prevent cerebral malaria. Int J Parasitol 37: 963–973. doi: 10.1016/j.ijpara.2007.01.004 17350019

28. Haque A, Best SE, Amante FH, Mustafah S, Desbarrieres L, et al. (2010) CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo. PLoS Pathog 6: e1001221. doi: 10.1371/journal.ppat.1001221 21170302

29. Brunner SM, Schiechl G, Falk W, Schlitt HJ, Geissler EK, et al. (2011) Interleukin-33 prolongs allograft survival during chronic cardiac rejection. Transpl Int 24: 1027–1039. doi: 10.1111/j.1432-2277.2011.01306.x 21797940

30. Turnquist HR, Zhao Z, Rosborough BR, Liu Q, Castellaneta A, et al. (2011) IL-33 expands suppressive CD11b+ Gr-1(int) and regulatory T cells, including ST2L+ Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival. J Immunol 187: 4598–4610. doi: 10.4049/jimmunol.1100519 21949025

31. Jiang HR, Milovanovic M, Allan D, Niedbala W, Besnard AG, et al. (2012) IL-33 attenuates EAE by suppressing IL-17 and IFN-gamma production and inducing alternatively activated macrophages. Eur J Immunol 42: 1804–1814. doi: 10.1002/eji.201141947 22585447

32. Lahl K, Loddenkemper C, Drouin C, Freyer J, Arnason J, et al. (2007) Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med 204: 57–63. doi: 10.1084/jem.20061852 17200412

33. Steeg C, Adler G, Sparwasser T, Fleischer B, Jacobs T (2009) Limited role of CD4+Foxp3+ regulatory T cells in the control of experimental cerebral malaria. J Immunol 183: 7014–7022. doi: 10.4049/jimmunol.0901422 19890049

34. Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, et al. (2013) Innate lymphoid cells—a proposal for uniform nomenclature. Nat Rev Immunol 13: 145–149. doi: 10.1038/nri3365 23348417

35. Monticelli LA, Sonnenberg GF, Artis D (2012) Innate lymphoid cells: critical regulators of allergic inflammation and tissue repair in the lung. Curr Opin Immunol 24: 284–289. doi: 10.1016/j.coi.2012.03.012 22521139

36. Lawrence T, Natoli G (2011) Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 11: 750–761. doi: 10.1038/nri3088 22025054

37. Biswas SK, Mantovani A (2010) Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 11: 889–896. doi: 10.1038/ni.1937 20856220

38. Choi KM, Kashyap PC, Dutta N, Stoltz GJ, Ordog T, et al. (2010) CD206-positive M2 macrophages that express heme oxygenase-1 protect against diabetic gastroparesis in mice. Gastroenterology 138: 2399–2409, 2409 e2391. doi: 10.1053/j.gastro.2010.02.014 20178793

39. Cairo G, Recalcati S, Mantovani A, Locati M (2011) Iron trafficking and metabolism in macrophages: contribution to the polarized phenotype. Trends Immunol 32: 241–247. doi: 10.1016/j.it.2011.03.007 21514223

40. Pamplona A, Ferreira A, Balla J, Jeney V, Balla G, et al. (2007) Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nat Med 13: 703–710. doi: 10.1038/nm1586 17496899

41. Schiering C, Krausgruber T, Chomka A, Frohlich A, Adelmann K, et al. (2014) The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 513: 564–568. doi: 10.1038/nature13577 25043027

42. Buffet PA, Safeukui I, Deplaine G, Brousse V, Prendki V, et al. (2011) The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology. Blood 117: 381–392. doi: 10.1182/blood-2010-04-202911 20852127

43. Tamura T, Akbari M, Kimura K, Kimura D, Yui K (2014) Flt3 ligand treatment modulates parasitemia during infection with rodent malaria parasites via MyD88- and IFN-gamma-dependent mechanisms. Parasite Immunol 36: 87–99. doi: 10.1111/pim.12085 24400637

44. Stolarski B, Kurowska-Stolarska M, Kewin P, Xu D, Liew FY (2010) IL-33 exacerbates eosinophil-mediated airway inflammation. J Immunol 185: 3472–3480. doi: 10.4049/jimmunol.1000730 20693421

45. Waters LS, Taverne J, Tai PC, Spry CJ, Targett GA, et al. (1987) Killing of Plasmodium falciparum by eosinophil secretory products. Infect Immun 55: 877–881. 3549562

46. Couper KN, Blount DG, Wilson MS, Hafalla JC, Belkaid Y, et al. (2008) IL-10 from CD4CD25Foxp3CD127 adaptive regulatory T cells modulates parasite clearance and pathology during malaria infection. PLoS Pathog 4: e1000004. doi: 10.1371/journal.ppat.1000004 18401464

47. Walther M, Jeffries D, Finney OC, Njie M, Ebonyi A, et al. (2009) Distinct roles for FOXP3 and FOXP3 CD4 T cells in regulating cellular immunity to uncomplicated and severe Plasmodium falciparum malaria. PLoS Pathog 5: e1000364. doi: 10.1371/journal.ppat.1000364 19343213

48. Fauconnier M, Bourigault ML, Meme S, Szeremeta F, Palomo J, et al. (2011) Protein kinase C-theta is required for development of experimental cerebral malaria. Am J Pathol 178: 212–221. doi: 10.1016/j.ajpath.2010.11.008 21224058