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United States Department of Agriculture

Agricultural Research Service

Title: Infection with Foot-and-Mouth Disease Virus Causes Loss of Circulating Plasmacytoid Dendritic Cells and Abrogates the Interferon Alpha Response to Tlr Agonists

Authors
item Golde, William
item Nfon, Charles - ORISE, ARS PIADC FELLOW

Research conducted cooperatively with:
item Merial Limited

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: September 1, 2006
Publication Date: September 16, 2006
Citation: Golde, W.T., Nfon, C. 2006. Infection with Foot-and-Mouth Disease Virus Causes Loss of Circulating Plasmacytoid Dendritic Cells and Abrogates the Interferon Alpha Response to TLR Agonists. 9th International Conference on Dendritic Cells, September 16, 2006. Poster 4.022, P.89.

Technical Abstract: Immune evasion by pathogens is often critical to virulence and spread of the infectious agent. Foot-and-mouth disease virus (FMDV) is considered one of the most contagious infections known yet is very sensitive to both type I and type II interferons (IFN). In many species including swine, plasmacytoid dendritic cells (pDC) are natural interferon producing cells, sensing and responding to pathogens and pathogen associated molecular pattern molecules (PAMPs) by secreting large amounts of interferon alpha. Mechanisms of evading IFN responses by FMDV previously reported are related to virally derived proteases that arrest host cell protein translation and transcriptional activation of IFN gene expression in the infected cell. However, we have reported that PBMC (peripheral blood mononuclear cells) are not productively infected during acute viremia when viral load can be very high (106/ml). During this period there is massive shedding of the virus resulting in the rapid spread of infection. Further, we have also shown that peak viremia is characterized by lymphopenia and suppressed T cell proliferative responses and depressed IFN'gamma responses within the persisting lymphocyte population. Here, we now report the response of pDC to the type A CpG formulation, 2216. This TLR 9 agonist stimulates porcine pDC to high levels of IFN'alpha secretion assayed by either ELISA for protein or ELISpot for cells. These pDC show a significant decline in PBMC during the first few days of infection with FMDV. In addition, IFN alpha levels in CpG stimulated PBMC supernatants declined in a similar manner to pDC numbers, with the minimum levels of cells and secreted IFN'alpha corresponding to peaks in viremia. These results indicate that the FMD virus has evolved the capacity to evade innate immunity through induction of a general lymphopenia, notably reducing T cell and pDC numbers, important sources of IFN in the circulation. In addition, innate immune responses in the form of IFN'alpha'secretion by pDC, are inhibited. Further elucidation of the mechanisms FMDV immune evasion will aid in the better development and use of FMDV vaccines and antivirals.

Last Modified: 10/20/2014
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