Natural killer cells display impaired responses to toll like receptor 9 that support viral persistence in chronic hepatitis B

Abstract

Toll like receptors (TLR) are crucial mediators of innate immune responses, but their influence on natural killer (NK) cell function in chronic hepatitis B infection (CHB) is not well understood. Here we evaluated the responses of peripheral NK cells from CHB patients to multiple TLR agonists. CHB was associated with an impaired NK cell IFN-γ response to TLR9 stimulation compared to controls. This deficiency corrected with recombinant IFN-alpha, while anti-IFN-alpha neutralizing antibody diminished NK IFN-γ production in controls. NK cell CD69 upregulation in response to TLR9 was maintained in CHB. No differences were noted in responses to the other TLR ligands. Our results demonstrate a dic..