Human cytomegalovirus IL-10 augments NK cell cytotoxicity.
J Leukoc Biol
; 106(2): 447-454, 2019 08.
Article
in En
| MEDLINE
| ID: mdl-30964577
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Killer Cells, Natural
/
Cytomegalovirus Infections
/
Cytomegalovirus
/
Cytotoxicity, Immunologic
/
Host-Pathogen Interactions
Limits:
Humans
Language:
En
Journal:
J Leukoc Biol
Year:
2019
Document type:
Article
Affiliation country:
Canada