NK cells in host responses to viral infections

Abstract

Natural killer (NK) cells are cytotoxic innate lymphocytes that play an important role in viral clearance. NK cell responses to viral infections were originally believed to be non-specific and lacked immune memory recall responses. It is now appreciated that NK cell responses to viral infections can be specific and in some cases memory recall responses are established. Increasing evidence also illuminates the complexity of NK cell interactions with both innate and adaptive immune cells. Here, we summarize the evidence for NK cell-specific memory responses to viral infections and the intricate reciprocal interactions between NK cells and other immune cells that dictate their activation and effector functions.

Figure 1. Expansion of NK cells in cytomegalovirus infection

Ly49H-m157 interaction in MCMV infection (A) and CD94-NKG2C and HLA-E interaction in HCMV infection (B) induces NK cell production of IFN-γ and lysis of target cell. NK cells persist as memory cells. (C) Synergy of CD2 and CD16 for effective antibody-dependent cell-mediated cytotoxicity (ADCC) of HCMV-infected cells in KLRC2^−/− humans.

Figure 2. NK cell interactions and their effects on other immune cells

NK cells modulate other immune cells to coordinate anti-viral immune responses. Interactions with neutrophils, macrophages, monocytes, and dendritic cells results in mutual activation or NK cell-mediated lysis to limit responses. NK cells directly or indirectly modulate CD4⁺ and CD8⁺ T cell responses.