Infection with foot-and-mouth disease virus induces a natural killer cell response in cattle (P6080)

Abstract

Abstract Natural killer (NK) cells play an important role in innate immune defense against viral diseases. Although they develop from the same lymphoid precursor cells as B and T lymphocytes, NK cells lack an antigen specific receptor, and are regulated in an antigen-independent manner yet have effector functions similar to T cells. The activation state of NK cells is determined by the balance of activating and inhibitory signals transmitted through surface receptors. Target cell expression of MHC class I serves as a powerful inhibitory signal for NK cells. Foot-and-mouth disease (FMD) is a viral disease of cloven-hoofed animals that is of particular concern for livestock species including cattle, swine, sheep, and goats. Clinical disease is characterized by fever, viremia, and the presence of vesicles in the mouth and on the feet and teats. FMD virus (FMDV) has evolved several immune-evading characteristics, including inhibition of MHC class I surface expression. Although this loss of class I MHC expression would be expected to result in NK cell activation during FMDV infection, swine with FMD exhibit a loss of NK cell function that cannot be overcome by ex vivo cytokine stimulation. Here we show that, in contrast to swine, FMDV-infected cattle exhibit an increase in NK cell cytolytic activity that is accompanied by an early and brief increase in NK-like cytolysis by γδ T cells. These data represent a difference in disease pathogenesis between these two susceptible species.