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Title: Effect of foot-and-mouth disease virus infection on the frequency, phenotype and function of circulating dendritic cells in cattle

Author
item SEI, JANET - Oak Ridge Institute For Science And Education (ORISE)
item WATERS, RYAN - Oak Ridge Institute For Science And Education (ORISE)
item Kenney, Mary
item BARLOW, JOHN - University Of Vermont
item Golde, William

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2016
Publication Date: 3/23/2016
Citation: Sei, J., Waters, R., Kenney, M.A., Barlow, J., Golde, W.T. 2016. Effect of foot-and-mouth disease virus infection on the frequency, phenotype and function of circulating dendritic cells in cattle. PLoS One. 11(3):e0152192.

Interpretive Summary: Cloven-hoofed animals such as cattle, pigs, sheep, and goats are important food sources for majority of the world. However, these animals are highly susceptible to foot-and-mouth virus (FMDV), which causes a debilitating disease characterized by development of blisters on their mouth and hooves, high fever, and lethargy. This high morbidity causes considerable economic loss to the agricultural industry. When these animals are infected, FMDV rapidly replicates, disseminates systemically, and sheds into the environment, infecting other susceptible animals. Dendritic cells (DC) are natural immune cells that play a role in limiting the spread of virus within a host. Therefore, during acute FMDV infection of cattle, we investigated the function of circulating DC in the blood. We report that while the frequency of DC increased at 3 to 4 days after FMDV infection, cells from these cattle displayed decreased function. These included abnormally low levels of white blood cells called lymphocytes, decreased activation of a broader immune response and increased inhibition of inflammatory cells. All these data suggests that FMDV impedes the function of DC, thereby easing its spread systemically, and then to susceptible animals.

Technical Abstract: Foot-and-mouth disease virus (FMDV) is a highly contagious virus that causes one of the most devastating diseases in cloven-hoofed animals. Disease symptoms in FMDV-infected animals appear within 2 to 3 days of exposure. Dendritic cells (DC) play an essential role in protective immune responses against pathogens. Therefore, investigating their role during FMDV infection, would lead to a better understanding on host-pathogen interactions. In this study, following infection of cattle with FMDV, we investigated the frequency and function of blood conventional (cDC) and plasmacytoid DC (pDC). We show that the frequency of cDC and pDC increased following FMDV infection, and peaked 3 to 4 days post-infection. During peak viremia, the cattle became lymphopenic, expression of MHC class II molecules on cDC and pDC was dramatically down-regulated, processing of exogenous antigen by cDC and pDC was inhibited, and an increase in IL-10 production by DC and monocytes was detected. Notably, after clearance of FMDV from the blood, MHC class II levels returned to pre-infection levels. Altogether, our study demonstrates that in cattle, FMDV inhibits the function of DC, thereby retarding the initiation of adaptive immune responses, thus allowing it to shed into the environment.