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

2.50
Hdl Handle:
http://hdl.handle.net/10033/620975
Title:
IL-33/ST2 pathway drives regulatory T cell dependent suppression of liver damage upon cytomegalovirus infection.
Authors:
Popovic, Branka; Golemac, Mijo; Podlech, Jürgen; Zeleznjak, Jelena; Bilic-Zulle, Lidija; Lukic, Miodrag L; Cicin-Sain, Luka ( 0000-0003-3978-778X ) ; Reddehase, Matthias J; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Krmpotic, Astrid; Jonjic, Stipan
Abstract:
Regulatory T (Treg) cells dampen an exaggerated immune response to viral infections in order to avoid immunopathology. Cytomegaloviruses (CMVs) are herpesviruses usually causing asymptomatic infection in immunocompetent hosts and induce strong cellular immunity which provides protection against CMV disease. It remains unclear how these persistent viruses manage to avoid induction of immunopathology not only during the acute infection but also during life-long persistence and virus reactivation. This may be due to numerous viral immunoevasion strategies used to specifically modulate immune responses but also induction of Treg cells by CMV infection. Here we demonstrate that liver Treg cells are strongly induced in mice infected with murine CMV (MCMV). The depletion of Treg cells results in severe hepatitis and liver damage without alterations in the virus load. Moreover, liver Treg cells show a high expression of ST2, a cellular receptor for tissue alarmin IL-33, which is strongly upregulated in the liver of infected mice. We demonstrated that IL-33 signaling is crucial for Treg cell accumulation after MCMV infection and ST2-deficient mice show a more pronounced liver pathology and higher mortality compared to infected control mice. These results illustrate the importance of IL-33 in the suppressive function of liver Treg cells during CMV infection.
Affiliation:
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen Str.7, 30625 Hannover, Germany.
Citation:
IL-33/ST2 pathway drives regulatory T cell dependent suppression of liver damage upon cytomegalovirus infection. 2017, 13 (4):e1006345 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Apr-2017
URI:
http://hdl.handle.net/10033/620975
DOI:
10.1371/journal.ppat.1006345
PubMed ID:
28448566
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the research group immune aging and chronic infections (IMCI); publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorPopovic, Brankaen
dc.contributor.authorGolemac, Mijoen
dc.contributor.authorPodlech, Jürgenen
dc.contributor.authorZeleznjak, Jelenaen
dc.contributor.authorBilic-Zulle, Lidijaen
dc.contributor.authorLukic, Miodrag Len
dc.contributor.authorCicin-Sain, Lukaen
dc.contributor.authorReddehase, Matthias Jen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorKrmpotic, Astriden
dc.contributor.authorJonjic, Stipanen
dc.date.accessioned2017-06-22T12:40:02Z-
dc.date.available2017-06-22T12:40:02Z-
dc.date.issued2017-04-
dc.identifier.citationIL-33/ST2 pathway drives regulatory T cell dependent suppression of liver damage upon cytomegalovirus infection. 2017, 13 (4):e1006345 PLoS Pathog.en
dc.identifier.issn1553-7374-
dc.identifier.pmid28448566-
dc.identifier.doi10.1371/journal.ppat.1006345-
dc.identifier.urihttp://hdl.handle.net/10033/620975-
dc.description.abstractRegulatory T (Treg) cells dampen an exaggerated immune response to viral infections in order to avoid immunopathology. Cytomegaloviruses (CMVs) are herpesviruses usually causing asymptomatic infection in immunocompetent hosts and induce strong cellular immunity which provides protection against CMV disease. It remains unclear how these persistent viruses manage to avoid induction of immunopathology not only during the acute infection but also during life-long persistence and virus reactivation. This may be due to numerous viral immunoevasion strategies used to specifically modulate immune responses but also induction of Treg cells by CMV infection. Here we demonstrate that liver Treg cells are strongly induced in mice infected with murine CMV (MCMV). The depletion of Treg cells results in severe hepatitis and liver damage without alterations in the virus load. Moreover, liver Treg cells show a high expression of ST2, a cellular receptor for tissue alarmin IL-33, which is strongly upregulated in the liver of infected mice. We demonstrated that IL-33 signaling is crucial for Treg cell accumulation after MCMV infection and ST2-deficient mice show a more pronounced liver pathology and higher mortality compared to infected control mice. These results illustrate the importance of IL-33 in the suppressive function of liver Treg cells during CMV infection.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleIL-33/ST2 pathway drives regulatory T cell dependent suppression of liver damage upon cytomegalovirus infection.en
dc.typeArticleen
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen Str.7, 30625 Hannover, Germany.en
dc.identifier.journalPLoS pathogensen

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