Title

Type I Interferons Link Viral Infection to Enhanced Epithelial Turnover and Repair

Document Type

Article

Language

eng

Format of Original

13 p.

Publication Date

1-2015

Publisher

Elsevier

Source Publication

Cell Host & Microbe

Source ISSN

1931-3128

Abstract

The host immune system functions constantly to maintain chronic commensal and pathogenic organisms in check. The consequences of these immune responses on host physiology are as yet unexplored, and may have long-term implications in health and disease. We show that chronic viral infection increases epithelial turnover in multiple tissues, and the antiviral cytokines type I interferons (IFNs) mediate this response. Using a murine model with persistently elevated type I IFNs in the absence of exogenous viral infection, the Irgm1−/− mouse, we demonstrate that type I IFNs act through nonepithelial cells, including macrophages, to promote increased epithelial turnover and wound repair. Downstream of type I IFN signaling, the highly related IFN-stimulated genes Apolipoprotein L9a and b activate epithelial proliferation through ERK activation. Our findings demonstrate that the host immune response to chronic viral infection has systemic effects on epithelial turnover through a myeloid-epithelial circuit.

Comments

Cell Host & Microbe, Vol. 17, No. 1 (January 2015): 85-97. DOI.

Sofia Origanti was affiliated with Washington University School of Medicine at the time of publication.