Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide Journal Article
| Authors: | Madera, S.; Rapp, M.; Firth, M. A.; Beilke, J. N.; Lanier, L. L.; Sun, J. C. |
| Article Title: | Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide |
| 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-alpha 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. |
| Keywords: | gene; dendritic cells; receptor; interferon-alpha; activation; responses; natural-killer-cells; cd8(+) t-cells; antiviral defense; regulatory factor-2 |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 213 |
| Issue: | 2 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2016-02-08 |
| Start Page: | 225 |
| End Page: | 233 |
| Language: | English |
| ACCESSION: | WOS:000373383700009 |
| DOI: | 10.1084/jem.20150712 |
| PROVIDER: | wos |
| PMCID: | PMC4749923 |
| PUBMED: | 26755706 |
| Notes: | Article -- Source: Wos |
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