Here today – not gone tomorrow: Roles for activating receptors in sustaining NK cells during viral infections

Abstract

The conclusive evidence supporting a role for NK cells in defense against viruses has been obtained under conditions of NK cell deficiencies prior to infections. NK cell proliferation can be induced during infections, but the advantages of resulting expansion have been unclear because NK cell basal frequency is already high. However, NK cell decreases are also observed during certain conditions of viral infection. Given the range of potent antiviral and immunoregulatory functions of NK cells, such “disappearance” dramatically changes the resources available to the host. New studies demonstrate that proliferation dependent on activating receptors for virus-induced ligands is key for NK cell maintenance, and allows their continued availability for control of adaptive immune responses and immunopathology. This pathway for sustaining NK cells may represent a system used generally to select subsets for rescue during homeostatic purging. In the case of NK cells, though, nonselection limits continued access to the many beneficial functions of NK cells. The observations resolve the long-standing conundrum of reported NK cell increases and decreases during viral infections. Moreover, they demonstrate a previously unappreciated role for activating receptors, i.e. to keep NK cells here today and also tomorrow.

Genetic Labeling Reveals Altered Turnover and Stability of Innate Lymphocytes in Latent Mouse Cytomegalovirus Infection

“…This process could either depend on specific late "NK epitopes" expressed by MCMV on its way to latency or could be induced by other factors such as homeostatic cytokines. Current reports on m157-reactive Ly49H + NK cells in C57BL/6 mice often designate receptor-dependent skewing of NK lymphocyte populations as "NK cell memory" (27,31). Reminiscent of CD8 + memory T cells, these NK cells become long-lived after an initial phase of proliferation (12,29,31).…”

Natural Killer Cell Responses to Viral Infection

“…IFN-␥ exerts direct effects in making host cells less hospitable to the virus and can act distally to prevent infection in other cells. It also recruits and activates other effector leukocytes, including cytotoxic T lymphocytes and CD4 + T helper type 1 cells [59] . NK cell production of IFN-␥ helps to control MCMV.…”

The anti-canine distemper virus activities of ex vivo-expanded canine natural killer cells

“…Important antiviral effects include direct killing of infected cells and production of cytokines exhibiting antiviral activity (Lee and Biron, 2010;Vidal et al, 2011;Zhang et al, 2010). However, little has been published on the NK cell defenses active against severe virus infections, such as CDV infection of dogs.…”