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Mediators of Inflammation
Volume 2017 (2017), Article ID 1359064, 15 pages
Research Article

Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis

1Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, France
2Université de Rennes 1, 35043 Rennes, France
3Structure Fédérative BioSit UMS 3480, CNRS-US18-INSERM, 35043 Rennes, France
4Service de Biochimie CHU Rennes, Université de Rennes 1, Rennes, France
5Institut de Génétique et Développement de Rennes (IGDR), UMR 6290 CNRS, Université de Rennes 1, 35043 Rennes, France
6Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique (IPBS-CNRS), Université de Toulouse, 31077 Toulouse, France
7Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, QC, Canada

Correspondence should be addressed to Michel Samson

Received 17 October 2016; Revised 7 March 2017; Accepted 16 March 2017; Published 21 May 2017

Academic Editor: Alex Kleinjan

Copyright © 2017 Virginie Carrière et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.