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Title: CONSTITUTIVE EXPRESSION OF IFN-ALPHA BY PORCINE SKIN DENDRITIC CELLS CONFERS RESISTANCE TO INFECTION BY FOOT-AND-MOUTH DISEASE VIRUS (FMDV)

Author
item Bautista Peck, Elida
item Ferman Ii, Geoffrey
item Gregg, Douglas
item BRUM, MARIO - FED UNIV SANTA MARIA BZ
item Grubman, Marvin
item Golde, William

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/19/2004
Publication Date: 4/1/2005
Citation: Bautista Peck, E.M., Ferman Ii, G.S., Gregg, D.A., Brum, M.C., Grubman, M.J., Golde, W.T. 2005. Constitutive Expression of IFN-alpha by Porcine Skin Dendritic Cells Confers Resistance to Infection by Foot-and-Mouth Disease Virus (FMDV). Journal of Virology 79 (8). P 4838-4847.

Interpretive Summary: Dendritic cells are now known to be very important in many aspects of the immune response to pathogens. These cells are critical in the rapid, nonspecific innate response as well as the long lasting and very specific adaptive immune response. Little is known about the role these cells play in the immune response to FMDV in livestock species. We investigated whether these cells are a target of viral infection or whether they play a role in fighting that infection. Results clearly show that dendritic cells resident in the skin of swine are resistant to infection with FMDV and constitutively express the anti-viral protein, interferon alpha. This appears to be a very unique and very important characteristic of skin derived dendritic cells.

Technical Abstract: The role of dendritic cells (DC) in the initiation of immune responses against foot-and-mouth disease virus (FMDV) is poorly understood. We analyzed the innate response of freshly isolated swine skin DC to the virus and show a rapid induction of interferon beta (IFN-beta) mRNA but not IFN-alpha mRNA. However, these DC secrete both IFN alpha and IFN beta protein in response to live virus but not killed virus. Further, surface expression of swine MHC Class II (SLA II) or CD80/CD86 molecules and antigen processing functions were not affected by FMDV exposure. Given the demonstrated sensitivity of FMDV to Type I interferons, there was no productive or nonproductive infection of these cells. Finally, freshly isolated skin DC constitutively express intracellular IFN alpha protein in the absence of stimulation with no detectable secretion of the cytokine until virus exposure. In situ analysis of these DC shows these cells express and store IFN alpha in uninfected animals. This is the first demonstration of constitutive expression of Type I interferon in resident, tissue derived DC and indicates that skin DC can play an important role in the innate immune response of swine to viral infections.