Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide.
Web of Science
AuthorMadera, S; Rapp, M; Firth, MA; Beilke, JN; Lanier, LL; Sun, JC
Source TitleJournal of Experimental Medicine
PublisherRockefeller University Press
University of Melbourne Author/sFirth, Matthew
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsMadera, S., Rapp, M., Firth, M. A., Beilke, J. N., Lanier, L. L. & Sun, J. C. (2016). Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide.. J Exp Med, 213 (2), pp.225-233. https://doi.org/10.1084/jem.20150712.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749923
Type I interferon (IFN) is crucial in host antiviral defense. Previous studies have described the pleiotropic role of type I IFNs on innate and adaptive immune cells during viral infection. Here, we demonstrate that natural killer (NK) cells from mice lacking the type I IFN-α receptor (Ifnar(-/-)) or STAT1 (which signals downstream of IFNAR) are defective in expansion and memory cell formation after mouse cytomegalovirus (MCMV) infection. Despite comparable proliferation, Ifnar(-/-) NK cells showed diminished protection against MCMV infection and exhibited more apoptosis compared with wild-type NK cells. Furthermore, we show that Ifnar(-/-) NK cells express increased levels of NK group 2 member D (NKG2D) ligands during viral infection and are susceptible to NK cell-mediated fratricide in a perforin- and NKG2D-dependent manner. Adoptive transfer of Ifnar(-/-) NK cells into NK cell-deficient mice reverses the defect in survival and expansion. Our study reveals a novel type I IFN-dependent mechanism by which NK cells evade mechanisms of cell death after viral infection.
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