Type i interferons link viral infection to enhanced epithelial turnover and repair

Lulu Sun, Hiroyuki Miyoshi, Sofia Origanti, Timothy J. Nice, Alexandra C. Barger, Nicholas A. Manieri, Leslie A. Fogel, Anthony R. French, David Piwnica-Worms, Helen Piwnica-Worms, Herbert W. Virgin, Deborah J. Lenschow, Thaddeus S. Stappenbeck

Research output: Contribution to journalArticle

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)85-97
Number of pages13
JournalCell Host and Microbe
Volume17
Issue number1
DOIs
StatePublished - Jan 14 2015

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Fingerprint Dive into the research topics of 'Type i interferons link viral infection to enhanced epithelial turnover and repair'. Together they form a unique fingerprint.

  • Cite this

    Sun, L., Miyoshi, H., Origanti, S., Nice, T. J., Barger, A. C., Manieri, N. A., Fogel, L. A., French, A. R., Piwnica-Worms, D., Piwnica-Worms, H., Virgin, H. W., Lenschow, D. J., & Stappenbeck, T. S. (2015). Type i interferons link viral infection to enhanced epithelial turnover and repair. Cell Host and Microbe, 17(1), 85-97. https://doi.org/10.1016/j.chom.2014.11.004