|Diaz-San Segundo, Fayna - ORISE-ARS,PIADC FELLOW|
|De Los Santos, Teresa|
|Dawson, Harry - USDA,ARS, BARC|
Submitted to: European Study Group on the Molecular Biology of Picornaviruses
Publication Type: Abstract Only
Publication Acceptance Date: April 1, 2008
Publication Date: May 26, 2008
Citation: Diaz-San Segundo, F., Moraes, M., De Los Santos, T., Pacheco Tobin, J., Koster, M.J., Dawson, H., Golde, W.T., Grubman, M.J. 2008. Type I and II Interferons Activate the Innate Immune System to Promote Early Protection of Swine Against Foot-and-Mouth Disease Virus. European Study Group on the Molecular Biology of Picornaviruses. P 149 Technical Abstract: We have demonstrated that the synergistic action of type I and II interferons (IFN) can rapidly protect swine against challenge with a low dose of foot-and-mouth disease virus (FMDV). Protection correlated with an upregulation of some IFN stimulated genes (ISGs), including IP-10, INDO, and OAS in PBMCs. To gain a more comprehensive understanding of the mechanism of protection stimulated by IFNs we extended our studies to include the analysis of the ISGs in skin and the characterization of different cell types recruited to the skin. For this purpose, four groups of pigs were inoculated with different combinations of IFNs using an adenovirus vector (Ad5): 10^8 pfu Ad5-pIFN alpha in combination with 10^9 or 10^10 pfu Ad5-pIFN gamma (low and high combination groups), 10^10 pfu Ad5-pIFN gamma alone, and 10^10 pfu of a control Ad5. One day later all groups were challenged with a high dose of FMDV and the animals were biopsied in the heel bulb at various times pre- and post-challenge. With the high dose challenge, the IFNs did not confer sterile protection, although we observed a considerable delay in the onset of disease. However, we could correlate partial protection with an upregulation of the same ISGs observed previously in PBMCs and with an upregulation in skin of OAS, CCR2 and CCL2. Interestingly, we observed an increase in the number of epidermal dendritic cells in the group which received pIFN gamma and was the most protected. To avoid the stress caused by multiple biopsies, we performed an additional experiment using similar groups and included a PBS inoculated control group. Groups of 2 animals were euthanized at 1, 2 and 7 days post IFN inoculation. Cytokine gene and protein expression profiles and characterization of immune cell types from PBMCs, skin, and lymphoid tissues, will be examined. The results of these experiments will be discussed.