IL-33/ST2 pathway drives regulatory T cell dependent suppression of liver damage upon cytomegalovirus infection

PLoS Pathogens

Volumn 13, Issue 4, 2017, Pages

  Popovic, Branka ^a   Golemac, Mijo ^a   Podlech, Jürgen ^b   Zeleznjak, Jelena ^a   Bilic Zulle, Lidija ^c   Lukic, Miodrag L ^d   Cicin Sain, Luka ^e   Reddehase, Matthias J ^b   Sparwasser, Tim ^f   Krmpotic, Astrid ^a   Jonjic, Stipan ^a  

^a UNIVERSITY OF RIJEKA   (Croatia)

^b UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^c KBC RIJEKA   (Croatia)

^d UNIVERSITY OF KRAGUJEVAC   (Serbia)

^e HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^f INSTITUTE OF INFECTION IMMUNOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD28 ANTIGEN; GAMMA INTERFERON; GRANZYME B; INTERLEUKIN 1 RECEPTOR LIKE 1 PROTEIN; INTERLEUKIN 10; INTERLEUKIN 33; KI 67 ANTIGEN; PROTEIN BCL 2; TRANSCRIPTION FACTOR FOXP3; IL1RL1 PROTEIN, MOUSE; IL33 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL ISOLATION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTION; FLOW CYTOMETRY; HEPATITIS; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; LIVER INJURY; LIVER TISSUE; MORTALITY RATE; MOUSE; NONHUMAN; ORGAN CULTURE; PLAQUE ASSAY; PLAQUE FORMING CELL; PROTEIN EXPRESSION; RADIATION CHIMERA; REAL TIME POLYMERASE CHAIN REACTION; REGULATORY T LYMPHOCYTE; RNA EXTRACTION; ANIMAL; BAGG ALBINO MOUSE; C57BL MOUSE; CELL LINE; CELLULAR IMMUNITY; GENETICS; IMMUNOLOGY; LIVER; METABOLISM; MORTALITY; PATHOLOGY; SIGNAL TRANSDUCTION; VIROLOGY;

ANIMALS; CELL LINE; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; IMMUNITY, CELLULAR; INTERLEUKIN-1 RECEPTOR-LIKE 1 PROTEIN; INTERLEUKIN-33; LIVER; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; SIGNAL TRANSDUCTION; T-LYMPHOCYTES, REGULATORY;

EID: 85018289873     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1006345     Document Type: Article

References (64)

1. Josefowicz SZ, Lu LF, Rudensky AY, Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol. 2012;30:531–64. doi: 10.1146/annurev.immunol.25.022106.141623 22224781
2. Curotto de Lafaille MA, Lafaille JJ, Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor?Immunity. 2009;30(5):626–35. doi: 10.1016/j.immuni.2009.05.002 19464985
3. Cretney E, Kallies A, Nutt SL, Differentiation and function of Foxp3(+) effector regulatory T cells. Trends Immunol. 2013;34(2):74–80. doi: 10.1016/j.it.2012.11.002 23219401
4. Burzyn D, Benoist C, Mathis D, Regulatory T cells in nonlymphoid tissues. Nat Immunol. 2013;14(10):1007–13. PubMed Central PMCID: PMCPMC4708287. doi: 10.1038/ni.2683 24048122
5. Arpaia N, Green JA, Moltedo B, Arvey A, Hemmers S, Yuan S, et al. A Distinct Function of Regulatory T Cells in Tissue Protection. Cell. 2015;162(5):1078–89. PubMed Central PMCID: PMCPMC4603556. doi: 10.1016/j.cell.2015.08.021 26317471
6. Molofsky AB, Savage AK, Locksley RM, Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation. Immunity. 2015;42(6):1005–19. PubMed Central PMCID: PMCPMC4471869. doi: 10.1016/j.immuni.2015.06.006 26084021
7. Peine M, Marek RM, Löhning M, -33 in T Cell Differentiation, Function, and Immune Homeostasis. Trends Immunol. 2016.
8. Veiga-Parga T, Sehrawat S, Rouse BT, Role of regulatory T cells during virus infection. Immunol Rev. 2013;255(1):182–96. PubMed Central PMCID: PMCPMC3748387. doi: 10.1111/imr.12085 23947355
9. Lund JM, Hsing L, Pham TT, Rudensky AY, Coordination of early protective immunity to viral infection by regulatory T cells. Science. 2008;320(5880):1220–4. PubMed Central PMCID: PMCPMC2519146. doi: 10.1126/science.1155209 18436744
10. Ruckwardt TJ, Bonaparte KL, Nason MC, Graham BS, Regulatory T cells promote early influx of CD8+ T cells in the lungs of respiratory syncytial virus-infected mice and diminish immunodominance disparities. J Virol. 2009;83(7):3019–28. PubMed Central PMCID: PMCPMC2655550. doi: 10.1128/JVI.00036-09 19153229
11. Suvas S, Kumaraguru U, Pack CD, Lee S, Rouse BT, CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses. J Exp Med. 2003;198(6):889–901. PubMed Central PMCID: PMCPMC2194203. doi: 10.1084/jem.20030171 12975455
12. Zelinskyy G, Dietze KK, Hüsecken YP, Schimmer S, Nair S, Werner T, et al. The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response. Blood. 2009;114(15):3199–207. doi: 10.1182/blood-2009-03-208736 19671923
13. Belkaid Y, Rouse BT, Natural regulatory T cells in infectious disease. Nat Immunol. 2005;6(4):353–60. doi: 10.1038/ni1181 15785761
14. Lemmermann NA, Böhm V, Holtappels R, Reddehase MJ, In vivo impact of cytomegalovirus evasion of CD8 T-cell immunity: facts and thoughts based on murine models. Virus Res. 2011;157(2):161–74. doi: 10.1016/j.virusres.2010.09.022 20933556
15. Lisnić B, Lisnić VJ, Jonjić S, NK cell interplay with cytomegaloviruses. Curr Opin Virol. 2015;15:9–18. doi: 10.1016/j.coviro.2015.07.001 26208082
16. Jost NH, Abel S, Hutzler M, Sparwasser T, Zimmermann A, Roers A, et al. Regulatory T cells and T-cell-derived IL-10 interfere with effective anti-cytomegalovirus immune response. Immunol Cell Biol. 2014;92(10):860–71. doi: 10.1038/icb.2014.62 25070242
17. Lindenberg M, Solmaz G, Puttur F, Sparwasser T, Mouse cytomegalovirus infection overrules T regulatory cell suppression on natural killer cells. Virol J. 2014;11:145. PubMed Central PMCID: PMCPMC4254395. doi: 10.1186/1743-422X-11-145 25108672
18. Lokensgard JR, Schachtele SJ, Mutnal MB, Sheng WS, Prasad S, Hu S, Chronic reactive gliosis following regulatory T cell depletion during acute MCMV encephalitis. Glia. 2015. PubMed Central PMCID: PMCPMC4670295.
19. Terrazzini N, Bajwa M, Vita S, Cheek E, Thomas D, Seddiki N, et al. A novel cytomegalovirus-induced regulatory-type T-cell subset increases in size during older life and links virus-specific immunity to vascular pathology. J Infect Dis. 2014;209(9):1382–92. PubMed Central PMCID: PMCPMC3982844. doi: 10.1093/infdis/jit576 24203779
20. Walton SM, Wyrsch P, Munks MW, Zimmermann A, Hengel H, Hill AB, et al. The dynamics of mouse cytomegalovirus-specific CD4 T cell responses during acute and latent infection. J Immunol. 2008;181(2):1128–34. 18606665
21. Shevach EM, Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity. 2009;30(5):636–45. doi: 10.1016/j.immuni.2009.04.010 19464986
22. Schiering C, Krausgruber T, Chomka A, Fröhlich A, Adelmann K, Wohlfert EA, et al. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature. 2014;513(7519):564–8. doi: 10.1038/nature13577 25043027
23. Matta BM, Lott JM, Mathews LR, Liu Q, Rosborough BR, Blazar BR, et al. IL-33 is an unconventional Alarmin that stimulates IL-2 secretion by dendritic cells to selectively expand IL-33R/ST2+ regulatory T cells. J Immunol. 2014;193(8):4010–20. PubMed Central PMCID: PMCPMC4185240. doi: 10.4049/jimmunol.1400481 25217167
24. Jones CA, Congenital cytomegalovirus infection. Curr Probl Pediatr Adolesc Health Care. 2003;33(3):70–93. doi: 10.1067/mps.2003.3 12605193
25. Smith MA, Brennessel DJ, Cytomegalovirus. Infect Dis Clin North Am. 1994;8(2):427–38. 8089469
26. Krmpotic A, Bubic I, Polic B, Lucin P, Jonjic S, Pathogenesis of murine cytomegalovirus infection. Microbes Infect. 2003;5(13):1263–77. 14623023
27. Kohm AP, McMahon JS, Podojil JR, Begolka WS, DeGutes M, Kasprowicz DJ, et al. Cutting Edge: Anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells. J Immunol. 2006;176(6):3301–5. 16517695
28. Couper KN, Lanthier PA, Perona-Wright G, Kummer LW, Chen W, Smiley ST, et al. Anti-CD25 antibody-mediated depletion of effector T cell populations enhances susceptibility of mice to acute but not chronic Toxoplasma gondii infection. J Immunol. 2009;182(7):3985–94. PubMed Central PMCID: PMCPMC3942880. doi: 10.4049/jimmunol.0803053 19299696
29. Lahl K, Loddenkemper C, Drouin C, Freyer J, Arnason J, Eberl G, et al. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med. 2007;204(1):57–63. PubMed Central PMCID: PMCPMC2118432. doi: 10.1084/jem.20061852 17200412
30. Reddehase MJ, Rothbard JB, Koszinowski UH, A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes. Nature. 1989;337(6208):651–3. doi: 10.1038/337651a0 2465495
31. Holtappels R, Thomas D, Podlech J, Reddehase MJ, Two antigenic peptides from genes m123 and m164 of murine cytomegalovirus quantitatively dominate CD8 T-cell memory in the H-2d haplotype. J Virol. 2002;76(1):151–64. PubMed Central PMCID: PMCPMC135724. doi: 10.1128/JVI.76.1.151-164.2002 11739681
32. Bonilla WV, Fröhlich A, Senn K, Kallert S, Fernandez M, Johnson S, et al. The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses. Science. 2012;335(6071):984–9. doi: 10.1126/science.1215418 22323740
33. Le Goffic R, Arshad MI, Rauch M, L'Helgoualc'h A, Delmas B, Piquet-Pellorce C, et al. Infection with influenza virus induces IL-33 in murine lungs. Am J Respir Cell Mol Biol. 2011;45(6):1125–32. doi: 10.1165/rcmb.2010-0516OC 21642589
34. Orange JS, Salazar-Mather TP, Opal SM, Biron CA, Mechanisms for virus-induced liver disease: tumor necrosis factor-mediated pathology independent of natural killer and T cells during murine cytomegalovirus infection. J Virol. 1997;71(12):9248–58. PubMed Central PMCID: PMCPMC230227. 9371583
35. Trgovcich J, Stimac D, Polić B, Krmpotić A, Pernjak-Pugel E, Tomac J, et al. Immune responses and cytokine induction in the development of severe hepatitis during acute infections with murine cytomegalovirus. Arch Virol. 2000;145(12):2601–18. 11205107
36. Volarevic V, Mitrovic M, Milovanovic M, Zelen I, Nikolic I, Mitrovic S, et al. Protective role of IL-33/ST2 axis in Con A-induced hepatitis. J Hepatol. 2012;56(1):26–33. doi: 10.1016/j.jhep.2011.03.022 21703183
37. Jonjić S, Pavić I, Lucin P, Rukavina D, Koszinowski UH, Efficacious control of cytomegalovirus infection after long-term depletion of CD8+ T lymphocytes. J Virol. 1990;64(11):5457–64. PubMed Central PMCID: PMCPMC248597. 1976821
38. Tortorella D, Gewurz BE, Furman MH, Schust DJ, Ploegh HL, Viral subversion of the immune system. Annu Rev Immunol. 2000;18:861–926. doi: 10.1146/annurev.immunol.18.1.861 10837078
39. Chopra M, Biehl M, Steinfatt T, Brandl A, Kums J, Amich J, et al. Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion. J Exp Med. 2016;213(9):1881–900. Epub 2016/08/15. PubMed Central PMCID: PMCPMC4995078. doi: 10.1084/jem.20151563 27526711
40. Doherty PC, Zinkernagel RM, -cell-mediated immunopathology in viral infections. Transplant Rev. 1974;19(0):89–120. 4601807
41. Manigold T, Racanelli V, T-cell regulation by CD4 regulatory T cells during hepatitis B and C virus infections: facts and controversies. Lancet Infect Dis. 2007;7(12):804–13. doi: 10.1016/S1473-3099(07)70289-X 18045563
42. Livingston-Rosanoff D, Daley-Bauer LP, Garcia A, McCormick AL, Huang J, Mocarski ES, Antiviral T cell response triggers cytomegalovirus hepatitis in mice. J Virol. 2012;86(23):12879–90. PubMed Central PMCID: PMCPMC3497643. doi: 10.1128/JVI.01752-12 22993151
43. Arapović J, Arapović M, Golemac M, Traven L, Tomac J, Rumora D, et al. The specific NK cell response in concert with perforin prevents CD8(+) T cell-mediated immunopathology after mouse cytomegalovirus infection. Med Microbiol Immunol. 2015;204(3):335–44. doi: 10.1007/s00430-015-0409-y 25809566
44. Conroy H, Marshall NA, Mills KH, TLR ligand suppression or enhancement of Treg cells? A double-edged sword in immunity to tumours. Oncogene. 2008;27(2):168–80. doi: 10.1038/sj.onc.1210910 18176598
45. Turnquist HR, Zhao Z, Rosborough BR, Liu Q, Castellaneta A, Isse K, et al. 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. 2011;187(9):4598–610. PubMed Central PMCID: PMCPMC3197898. doi: 10.4049/jimmunol.1100519 21949025
46. Vasanthakumar A, Moro K, Xin A, Liao Y, Gloury R, Kawamoto S, et al. The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat Immunol. 2015;16(3):276–85. doi: 10.1038/ni.3085 25599561
47. Kuswanto W, Burzyn D, Panduro M, Wang KK, Jang YC, Wagers AJ, et al. Poor Repair of Skeletal Muscle in Aging Mice Reflects a Defect in Local, Interleukin-33-Dependent Accumulation of Regulatory T Cells. Immunity. 2016;44(2):355–67. PubMed Central PMCID: PMCPMC4764071. doi: 10.1016/j.immuni.2016.01.009 26872699
48. Matta BM, Reichenbach DK, Zhang X, Mathews L, Koehn BH, Dwyer GK, et al. Peri-alloHCT IL-33 administration expands recipient T-regulatory cells that protect mice against acute GVHD. Blood. 2016;128(3):427–39. Epub 2016/05/24. PubMed Central PMCID: PMCPMC4957164. doi: 10.1182/blood-2015-12-684142 27222477
49. Martin NT, Martin MU, Interleukin 33 is a guardian of barriers and a local alarmin. Nat Immunol. 2016;17(2):122–31. doi: 10.1038/ni.3370 26784265
50. Nabekura T, Girard JP, Lanier LL, IL-33 receptor ST2 amplifies the expansion of NK cells and enhances host defense during mouse cytomegalovirus infection. J Immunol. 2015;194(12):5948–52. PubMed Central PMCID: PMCPMC4458425. doi: 10.4049/jimmunol.1500424 25926677
51. Liesz A, Suri-Payer E, Veltkamp C, Doerr H, Sommer C, Rivest S, et al. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med. 2009;15(2):192–9. doi: 10.1038/nm.1927 19169263
52. Lu L, Li G, Rao J, Pu L, Yu Y, Wang X, et al. In vitro induced CD4(+)CD25(+)Foxp3(+) Tregs attenuate hepatic ischemia-reperfusion injury. Int Immunopharmacol. 2009;9(5):549–52. doi: 10.1016/j.intimp.2009.01.020 19539564
53. Kuboki S, Sakai N, Tschöp J, Edwards MJ, Lentsch AB, Caldwell CC, Distinct contributions of CD4+ T cell subsets in hepatic ischemia/reperfusion injury. Am J Physiol Gastrointest Liver Physiol. 2009;296(5):G1054–9. PubMed Central PMCID: PMCPMC2696215. doi: 10.1152/ajpgi.90464.2008 19264952
54. Arias-Diaz J, Ildefonso JA, Muñoz JJ, Zapata A, Jiménez E, Both tacrolimus and sirolimus decrease Th1/Th2 ratio, and increase regulatory T lymphocytes in the liver after ischemia/reperfusion. Lab Invest. 2009;89(4):433–45. doi: 10.1038/labinvest.2009.3 19188906
55. Townsend MJ, Fallon PG, Matthews DJ, Jolin HE, McKenzie AN, T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses. J Exp Med. 2000;191(6):1069–76. PubMed Central PMCID: PMCPMC2193113. 10727469
56. Wagner M, Jonjic S, Koszinowski UH, Messerle M, Systematic excision of vector sequences from the BAC-cloned herpesvirus genome during virus reconstitution. Journal of virology. 1999;73(8):7056–60. PubMed Central PMCID: PMC112796. 10400809
57. Jordan S, Krause J, Prager A, Mitrovic M, Jonjic S, Koszinowski UH, et al. Virus progeny of murine cytomegalovirus bacterial artificial chromosome pSM3fr show reduced growth in salivary Glands due to a fixed mutation of MCK-2. J Virol. 2011;85(19):10346–53. PubMed Central PMCID: PMCPMC3196435. doi: 10.1128/JVI.00545-11 21813614
58. Bubic I, Wagner M, Krmpotic A, Saulig T, Kim S, Yokoyama WM, et al. Gain of virulence caused by loss of a gene in murine cytomegalovirus. Journal of virology. 2004;78(14):7536–44. PubMed Central PMCID: PMC434107. doi: 10.1128/JVI.78.14.7536-7544.2004 15220428
59. Crnkovic-Mertens I, Messerle M, Milotic I, Szepan U, Kucic N, Krmpotic A, et al. Virus attenuation after deletion of the cytomegalovirus Fc receptor gene is not due to antibody control. Journal of virology. 1998;72(2):1377–82. PubMed Central PMCID: PMC124616. 9445038
60. Jonjic S, Krmpotic A, Arapovic J, Koszinowski UH, Dissection of the antiviral NK cell response by MCMV mutants. Methods Mol Biol. 2008;415:127–49. doi: 10.1007/978-1-59745-570-1_8 18370152
61. Podlech J, Holtappels R, Grzimek NKA, Reddehase MJ, Kaufmann SH, Kabelitz D, Animal models: murine cytomegalovirus. In: Methods in Microbiology: Immunology of Infection. London: Academic Press; 2002. p. 493–525.
62. Lemmermann NA, Podlech J, Seckert CK, Kropp KA, Grzimek NK, Reddehase MJ, Kabelitz D, Kaufmann SHE, et al. CD8 T-cell immunotherapy of cytomegalovirus disease in the murine model. In: Methods in Microbiology: Immunology of Infection. London: Academic Press; 2010. p. 369–420.
63. Lemmermann NA, Krmpotic A, Podlech J, Brizic I, Prager A, Adler H, et al. Non-redundant and redundant roles of cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread. PLoS Pathog. 2015;11(2):e1004640. Epub 2015/02/06. PubMed Central PMCID: PMCPMC4450070. doi: 10.1371/journal.ppat.1004640 25659098
64. Chiossone L, Audonnet S, Chetaille B, Chasson L, Farnarier C, Berda-Haddad Y, et al. Protection from inflammatory organ damage in a murine model of hemophagocytic lymphohistiocytosis using treatment with IL-18 binding protein. Front Immunol. 2012;3:239. Epub 2012/08/08. PubMed Central PMCID: PMCPMC3413989. doi: 10.3389/fimmu.2012.00239 22891066