| First Author | Anzaghe M | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1194733 | PubMed ID | 37720217 |
| Mgi Jnum | J:340785 | Mgi Id | MGI:7530148 |
| Doi | 10.3389/fimmu.2023.1194733 | Citation | Anzaghe M, et al. (2023) Interleukin-36gamma is causative for liver damage upon infection with Rift Valley fever virus in type I interferon receptor-deficient mice. Front Immunol 14:1194733 |
| abstractText | Type I interferons (IFN) are pro-inflammatory cytokines which can also exert anti-inflammatory effects via the regulation of interleukin (IL)-1 family members. Several studies showed that interferon receptor (IFNAR)-deficient mice develop severe liver damage upon treatment with artificial agonists such as acetaminophen or polyinosinic:polycytidylic acid. In order to investigate if these mechanisms also play a role in an acute viral infection, experiments with the Bunyaviridae family member Rift Valley fever virus (RVFV) were performed. Upon RVFV clone (cl)13 infection, IFNAR-deficient mice develop a severe liver injury as indicated by high activity of serum alanine aminotransferase (ALT) and histological analyses. Infected IFNAR(-/-) mice expressed high amounts of IL-36gamma within the liver, which was not observed in infected wildtype (WT) animals. In line with this, treatment of WT mice with recombinant IL-36gamma induced ALT activity. Furthermore, administration of an IL-36 receptor antagonist prior to infection prevented the formation of liver injury in IFNAR(-/-) mice, indicating that IL-36gamma is causative for the observed liver damage. Mice deficient for adaptor molecules of certain pattern recognition receptors indicated that IL-36gamma induction was dependent on mitochondrial antiviral-signaling protein and the retinoic acid-inducible gene-I-like receptor. Consequently, cell type-specific IFNAR knockouts revealed that type I IFN signaling in myeloid cells is critical in order to prevent IL-36gamma expression and liver injury upon viral infection. Our data demonstrate an anti-inflammatory role of type I IFN in a model for virus-induced hepatitis by preventing the expression of the novel IL-1 family member IL-36gamma. |
