Activation of Porcine Natural Killer Cells and Lysis of Foot-and-Mouth Disease Virus Infected Cells

Abstract

Natural killer (NK) cells play a vital role in innate response against viral infections and cellular transformation. In vivo modulation of their response may enhance their antiviral function. Here we describe the phenotype of porcine NK cells, test potential proinflammatory cytokines for activation of these cells and assess the capability of porcine NK cells to kill virus-infected or tumor cells in vitro. The CD2+/CD8+/CD3(-) cell compartment contained porcine NK cells, which at the resting stage were minimally cytotoxic toward foot-and-mouth disease virus (FMDV)-infected porcine cells or tumor cell lines. Direct stimulation of NK cells with proinflammatory cytokines induced efficient lysis of FMDV-infected cells with interleukin (IL)-2 or IL-15 showing the highest stimulatory capacity. Lower levels of NK cell activation were induced by IL-12, IL-18, or interferon (IFN)-alpha, however, IL-12 and IL-18 synergistically activated NK cells. Combinations of IL-15 and IL-12 or IL-15 and IL-18 did not further increase the porcine NK cell lytic capability over IL-15 alone. Natural killer cells expressed IFN-gamma regardless of the cytokine used for stimulation while expression of perforin increased modestly. The enhancement of porcine NK cell activity by proinflammatory cytokines offers a promising tool for development of antiviral approaches against virus infection.