PolyI:C plus IL-2 or IL-12 induce IFN-gamma production by human NK cells via autocrine IFN-beta.

ABSTRACT

NK lymphocytes and type I IFN (IFN-alpha/beta) are major actors of the innate anti-viral response that also influence adaptive immune responses. We evaluated type I IFN production by human NK cells in response to polyIC, a potent type I IFN-inducing TLR3 agonist. PolyIC plus IL-2/IL-12 induced IFN-beta (but not IFN-alpha) mRNA expression and protein production by highly pure human NK cells and by the human NK cell line NK92. Neutralizing anti-IFNAR1 or anti-IFN-beta Ab prevented the production of IFN-gamma induced by polyIC plus IL-2/IL-12. Similarly, IFN-gamma production induced by polyIC plus IL-12 was reduced in NK cells isolated from IFNAR1(-/-) compared with WT mice. The ability of polyIC plus IL-12 to induce IFN-gamma production was related to an increase of TLR3, Mda5 and IFNAR expression and by an increase of STAT1 and STAT4 phosphorylation. Collectively, these data demonstrate that NK cells, in response to polyIC plus IL-2/IL-12, produce IFN-beta that induce, in an autocrine manner, the production of IFN-gamma and thereby highlight that NK cells may control the outcome of protective or injurious immune responses through type I IFN secretion.