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

Cell Host Microbe. 2015 Jan 14;17(1):85-97. doi: 10.1016/j.chom.2014.11.004. Epub 2014 Dec 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology*
  • Epithelium / immunology*
  • Epithelium / physiology
  • Female
  • GTP-Binding Proteins / deficiency
  • Gene Expression Profiling
  • Interferon Type I / metabolism*
  • Male
  • Mice, Knockout
  • Molecular Sequence Data
  • Sequence Analysis, DNA
  • Signal Transduction
  • Virus Diseases / immunology*


  • Ifi1 protein, mouse
  • Interferon Type I
  • GTP-Binding Proteins

Associated data

  • GEO/GSE59603