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Human cytomegalovirus IL‐10 augments NK cell cytotoxicity
Author(s) -
Holder Kayla A.,
Grant Michael D.
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.2ab0418-158rr
Subject(s) - perforin , biology , nkg2d , degranulation , cd16 , human cytomegalovirus , cytotoxicity , interleukin 21 , natural killer cell , interleukin 12 , immunology , lymphokine activated killer cell , receptor , janus kinase 3 , microbiology and biotechnology , immune system , cytotoxic t cell , t cell , cd8 , virus , in vitro , cd3 , biochemistry
Human cytomegalovirus (HCMV) persistently infects most of the adult population with periods of productive and latent infection differentially orchestrated by multiple HCMV‐encoded gene products. One HCMV gene ( UL111a ) encodes cmvIL‐10, a virokine homologous to human IL (hIL)‐10. Although the effects of cmvIL‐10 on most human lymphocyte subsets have been extensively studied, its impact on NK cell function was unreported prior to this study. We investigated effects of short‐term cmvIL‐10 exposure on human NK cells and found it substantially enhanced NK cell cytotoxicity through natural cytotoxicity receptors NKp30 and NKp46 as well as through C‐type lectin‐like receptors NKG2C and NKG2D. Antibody‐dependent cell‐mediated cytotoxicity triggered through CD16 also increased significantly with short‐term cmvIL‐10 exposure. These effects of cmvIL‐10 on NK cell cytotoxicity were rapid, dose dependent, neutralized by polyclonal anti‐cmvIL‐10 or monoclonal anti‐IL‐10 receptor (IL‐10R) antibodies and independent of increased perforin synthesis or up‐regulation of activating receptors. A low percentage (0.5–5.4%; n = 12) of NK cells expressed IL‐10R and the impact of cmvIL‐10 on NK cells degranulation following CD16 stimulation directly correlated with this percentage ( P = 0.0218). Short‐term exposure of human NK cells to cmvIL‐10 did not introduce phenotypic changes reminiscent of NK adaptation to HCMV infection in vivo. Determining how expression of a viral protein that activates NK cells contributes to their function in vivo will increase understanding of HCMV infection and NK cell biology.