Protection against RNA-induced liver damage by myeloid cells requires type I interferon and IL-1 receptor antagonist in mice

Conrad E, Resch TK, Gogesch P, Kalinke U, Bechmann I, Bogdan C, Waibler Z (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Hepatology Wiley-Blackwell

Book Volume: 59

Pages Range: 1555-63

Journal Issue: 4

DOI: 10.1002/hep.26915

Abstract

Cell types and mechanisms involved in type I interferon (IFN)-mediated anti-inflammatory effects are poorly understood. Upon injection of artificial double-stranded RNA (poly(I:C)), we observed severe liver damage in type I IFN-receptor (IFNAR) chain 1-deficient mice, but not in wild-type (WT) controls. Studying mice with conditional IFNAR ablations revealed that IFNAR triggering of myeloid cells is essential to protect mice from poly(I:C)-induced liver damage. Accordingly, in poly(I:C)-treated WT, but not IFNAR-deficient mice, monocytic myeloid-derived suppressor cells (MDSCs) were recruited to the liver. Comparing WT and IFNAR-deficient mice with animals deficient for the IFNAR on myeloid cells only revealed a direct IFNAR-dependent production of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA) that could be assigned to liver-infiltrating cells. Upon poly(I:C) treatment, IFNAR-deficient mice displayed both a severe lack of IL-1RA production and an increased production of proinflammatory IL-1?, indicating a severely imbalanced cytokine milieu in the liver in absence of a functional type I IFN system. Depletion of IL-1? or treatment with recombinant IL-1RA both rescued IFNAR-deficient mice from poly(I:C)-induced liver damage, directly linking the deregulated IL-1? and IL-1RA production to liver pathology. Conclusion: Type I IFN signaling protects from severe liver damage by recruitment of monocytic MDSCs and maintaining a balance between IL-1? and IL-1RA production.

Authors with CRIS profile

Christian Bogdan Lehrstuhl für Mikrobiologie und Infektionsimmunologie

Involved external institutions

Universität Leipzig DE Germany (DE) Paul Ehrlich Institute / Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel (PEI) DE Germany (DE) Zentrum für Experimentelle und Klinische Infektionsforschung GmbH (TWINCORE) DE Germany (DE)

How to cite

APA:

Conrad, E., Resch, T.K., Gogesch, P., Kalinke, U., Bechmann, I., Bogdan, C., & Waibler, Z. (2014). Protection against RNA-induced liver damage by myeloid cells requires type I interferon and IL-1 receptor antagonist in mice. Hepatology, 59(4), 1555-63. https://doi.org/10.1002/hep.26915

MLA:

Conrad, Elea, et al. "Protection against RNA-induced liver damage by myeloid cells requires type I interferon and IL-1 receptor antagonist in mice." Hepatology 59.4 (2014): 1555-63.

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