Format

Send to

Choose Destination
J Exp Med. 2016 Feb 8;213(2):225-33. doi: 10.1084/jem.20150712. Epub 2016 Jan 11.

Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide.

Author information

1
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065 Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065.
2
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
3
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.
4
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065 Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065 sunj@mskcc.org.

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.

PMID:
26755706
PMCID:
PMC4749923
DOI:
10.1084/jem.20150712
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center