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Title: Early adaptive immune responses in the respiratory tract of foot and mouth disease-infected cattle

Author
item PEGA, J - Instituto Nacional Tecnologia Agropecuaria
item BUCAFUSCO, D - Instituto Nacional Tecnologia Agropecuaria
item DI GIACOMO, S - Instituto Nacional Tecnologia Agropecuaria
item MALACARI, D - Instituto Nacional Tecnologia Agropecuaria
item CAPOZZO, A - Instituto Nacional Tecnologia Agropecuaria
item Arzt, Jonathan
item PEREZ-BEASCOECHEA, C - National Health Service And Food Quality (SENASA)
item MARADEI, E - National Health Service And Food Quality (SENASA)
item Rodriguez, Luis
item Borca, Manuel
item PEREZ-FILGUEIRA, M - Instituto Nacional Tecnologia Agropecuaria

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2012
Publication Date: 12/19/2012
Citation: Pega, J., Bucafusco, D., Di Giacomo, S., Malacari, D., Capozzo, A., Arzt, J., Perez-Beascoechea, C., Maradei, E., Rodriguez, L.L., Borca, M.V., Perez-Filgueira, M. 2012. Early adaptive immune responses in the respiratory tract of foot and mouth disease-infected cattle. Journal of Virology. 87(5):2489-2495.

Interpretive Summary: Foot and mouth disease (FMD) is a highly contagious viral disease affecting a wide range of cloven hooved domestic and wild animals. The FMD virus (FMDV) acts very rapidly and causes disease 48-72 hours after infection. It is believed that the early local immune response by the infected animal defines the outcome of the infection. However, little is known about this phase of the disease. Here we analyzed the role of the early antibody responses induced infected cattle for their ability to limit or eliminate the infection. Animals infected using an aerosol exposure method developed previously in out laboratory had detectable FMDV-specific antibody producing immune cells in the respiratory tract and draining lymphatic organs as early as 5 days post infection. FMDV-specific antibodies were detected at the same time. The increase in antibodies coincided with a sharp decrease in virus in the blood, emphasizing the important role that antibody responses plays in clearing viral infection. The information generated here will be utilized to improve the immune response induced by FMD vaccines.

Technical Abstract: Foot and mouth disease (FMD) is a highly contagious viral disease which affects both domestic and wildlife biungulate species. This acute disease, caused by the FMD virus (FMDV), usually includes an active replication phase in the respiratory tract up to 72 h post-infection followed by hematogenous dissemination and vesicular lesions at oral and foot epithelia. The role of the early host local adaptive immunity in the outcome of the infection is not well understood. Here we report the kinetics of appearance of FMDV-specific antibody-secreting cells (ASC) in lymphoid organs along the respiratory tract and spleen in cattle infected by aerosol exposure. While no responses were observed up to 3 days post-infection (dpi), all animals developed FMDV-ASC in all the lymphoid organs studied at 4 dpi. Tracheobronchial lymph nodes were the most reactive organs at this time and IgM was the predominant isotype, followed by IgG1. Numbers of FMDV-ASC further augmented at 5 and 6 dpi with an increasing prevalence in upper respiratory organs. Systemic antibody responses were slightly delayed compared with the local reaction. Also, IgM was the dominant isotype in serum at 5 dpi, coinciding with a sharp decrease of viral RNA detection in peripheral blood. These results indicate that following aerogenous administration, cattle developed a rapid and vigorous genuine local antibody response throughout the respiratory tract. Time course and isotype profiles would indicate the presence of an efficient T-independent antibody response which drives the IgM-mediated virus clearance in cattle infected by FMDV aerosol exposure.