Infection with foot-and-mouth disease virus (FMDV) induces a natural killer (NK) cell response in cattle that is lacking following vaccination

Comp Immunol Microbiol Infect Dis. 2014 Sep;37(4):249-57. doi: 10.1016/j.cimid.2014.07.004. Epub 2014 Aug 12.

Abstract

Natural killer (NK) cells play a role in innate antiviral immunity by directly lysing virus-infected cells and producing antiviral cytokines such as interferon gamma (IFN-γ). We developed a system for characterizing the bovine NK response to foot-and-mouth disease virus (FMDV), which causes a disease of cloven-hoofed animals and remains a threat to livestock industries throughout the world. IL-2 stimulation of PBMC resulted in poor killing of human K562 cells, which are often used as NK target cells, while lysis of the bovine BL3.1 cell line was readily detected. Depletion of NKp46-expressing cells revealed that 80% of the killing induced by IL-2 could be attributed to NKp46(+) cells. In order to characterize the response of NK cells against FMDV in vivo, we infected groups of cattle with three different strains of the virus (A24 Cruzeiro, O1 Manisa, O Hong Kong) and evaluated the cytolytic ability of NK cells through the course of infection. We consistently observed a transient increase in cytolysis, although there was variation in magnitude and kinetics. This increase in cytolysis remained when CD3(+) cells were removed from the preparation of lymphocytes, indicating that cytolysis was independent of MHC-T cell receptor interaction or γδ T cell activation. In contrast, animals monitored following vaccination against FMDV did not exhibit any increase in NK killing. These data suggest that NK cells play a role in the host immune response of cattle against FMDV, and contrast with the suppression of NK activity previously observed in swine infected with FMDV.

Keywords: Cattle; FMDV; Infection; Innate immunity; Natural killer cells (NK); Vaccination.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Cell Line
  • Cytotoxicity, Immunologic
  • Foot-and-Mouth Disease / immunology*
  • Foot-and-Mouth Disease / metabolism
  • Foot-and-Mouth Disease Virus / immunology*
  • Humans
  • Interleukin-2 / metabolism
  • K562 Cells
  • Killer Cells, Natural / immunology*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / immunology
  • Lymphocyte Depletion
  • Lymphocytes / immunology
  • Viral Vaccines / immunology*

Substances

  • Interleukin-2
  • Viral Vaccines