Antibody-mediated response of NKG2Cbright NK cells against human cytomegalovirus.
Marcel Costa-GarciaAndrea VeraManuela MoraruCarlos VilchesMiguel López-BotetAura MuntasellPublished in: Journal of immunology (Baltimore, Md. : 1950) (2015)
Human CMV (HCMV) infection promotes a variable and persistent expansion of functionally mature NKG2C(bright) NK cells. We analyzed NKG2C(bright) NK cell responses triggered by Abs from HCMV(+) sera against HCMV-infected MRC5 fibroblasts. Specific Abs promoted the degranulation (i.e., CD107a expression) and the production of cytokines (TNF-α and IFN-γ) by a significant fraction of NK cells, exceeding the low natural cytotoxicity against HCMV-infected targets. NK cell-mediated Ab-dependent cell-mediated cytotoxicity was limited by viral Ag availability and HLA class I expression on infected cells early postinfection and increased at late stages, overcoming viral immunoevasion strategies. Moreover, the presence of specific IgG triggered the activation of NK cells against Ab-opsonized cell-free HCMV virions. As compared with NKG2A(+) NK cells, a significant proportion of NKG2C(bright) NK cells was FcεR γ-chain defective and highly responsive to Ab-driven activation, being particularly efficient in the production of antiviral cytokines, mainly TNF-α. Remarkably, the expansion of NKG2C(bright) NK cells in HCMV(+) subjects was related to the overall magnitude of TNF-α and IFN-γ cytokine secretion upon Ab-dependent and -independent activation. We show the power and sensitivity of the anti-HCMV response resulting from the cooperation between specific Abs and the NKG2C(bright) NK-cell subset. Furthermore, we disclose the proinflammatory potential of NKG2C(bright) NK cells, a variable that could influence the individual responses to other pathogens and tumors.
Keyphrases
- nk cells
- cell free
- endothelial cells
- rheumatoid arthritis
- poor prognosis
- dendritic cells
- sars cov
- immune response
- single cell
- epstein barr virus
- oxidative stress
- cell death
- cell therapy
- mesenchymal stem cells
- stem cells
- signaling pathway
- binding protein
- cell proliferation
- quantum dots
- cell cycle arrest
- cancer therapy
- circulating tumor cells
- circulating tumor
- climate change
- natural killer cells