1. Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide.
- Author
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Madera, Sharline, Rapp, Moritz, Firth, Matthew A, Beilke, Joshua N, Lanier, Lewis L, and Sun, Joseph C
- Subjects
Killer Cells ,Natural ,Animals ,Mice ,Inbred C57BL ,Mice ,Knockout ,Mice ,Muromegalovirus ,Herpesviridae Infections ,Interferon Type I ,Lymphocyte Activation ,Apoptosis ,Cell Proliferation ,STAT1 Transcription Factor ,Receptor ,Interferon alpha-beta ,Perforin ,NK Cell Lectin-Like Receptor Subfamily K ,Killer Cells ,Natural ,Inbred C57BL ,Knockout ,Receptor ,Interferon alpha-beta ,Immunology ,Medical and Health Sciences - Abstract
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.
- Published
- 2016