Location: Foreign Animal Disease ResearchTitle: Infection with foot-and-mouth disease virus (FMDV) induces a natural killer (NK) cell response in cattle that is lacking following vaccination Author
|Patch, Jared - University Of Vermont|
|Dar, Pervaiz - Indian Veterinary Research Institute|
|Waters, Ryan - Oak Ridge Institute For Science And Education (ORISE)|
|Toka, Felix - Warsaw University Of Life Sciences|
|Barerra, Jose - Us Deparment Of Homeland Security|
|Schutta, Christopher - Us Deparment Of Homeland Security|
|Kondabattula, Ganesh - Indian Veterinary Research Institute|
Submitted to: Comparative Immunology Microbiology and Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/28/2014
Publication Date: 8/12/2014
Citation: Patch, J.P., Dar, P., Waters, R., Toka, F., Barerra, J., Schutta, C., Kondabattula, G., Golde, W.T. 2014. Infection with foot-and-mouth disease virus (FMDV) induces a natural killer (NK) cell response in cattle that is lacking following vaccination. Comparative Immunology Microbiology and Infectious Diseases. 37(4):249-257.
Interpretive Summary: The immune response to both vaccination and infection involves the early, nonspecific innate immune response and the later, longer lasting and very specific adaptive immune response. We studied an aspect of innate immunity mediated by the “natural killer cell”, or NK cell. This unique cell, found in the blood, lymph nodes and spleen, can kill tumor cells or virus infected cells. We have previously shown that infection of swine with FMDV leads to a blocking of NK cell function in the infected animal. Here, we analyzed the function of NK cells of cattle following infection and vaccination. Inoculation of the standard FMDV vaccine (killed virus in oil adjuvant) showed no effect on NK cell function in the vaccinated cattle. In contrast, viral infection clearly resulted in activation of these cells. This activation was detected as early as 2 days after infection, and lasted for up to 7 days. These results may provide an explanation, at least in part, as to why pigs shed more virus during infection than cattle. In pigs the NK cell function is blocked. allowing virus to spread in the animal more readily. Contrarily, cattle NK cells are activated and likely help control virus infection in vivo, reducing viral load and shedding.
Technical 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 (IFNgamma). 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 most of the killing induced by IL-2 could be attributed to NK cells. In order to characterize the response of NK cells against FMDV in vivo, we infected groups of cattle with three different serotypes of the virus (A24, 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 CD3positive cells were removed from the preparation of lymphocytes, indicating that cytolysis was independent of MHC-T cell receptor interaction or gamma/delta 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.