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

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

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
5
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
6
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
7
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: stappenb@pathology.wustl.edu.

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.

Comment in

PMID:
25482432
PMCID:
PMC4297260
DOI:
10.1016/j.chom.2014.11.004
[Indexed for MEDLINE]
Free PMC Article
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