ARS | Publication request: UP-REGULATION OF INFLAMMATORY, REGULATORY AND TH1-IMMUNE MARKERS IN SWINE RESPONDING TO ACUTE TOXOPLASMA GONDII INFECTION.

Submitted to: American Association of Veterinary Parasitologists Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: June 20, 2005
Publication Date: July 5, 2005
Citation: Nishi, S.M., Dawson, H.D., Kuhar, D.J., Dubey, J.P., Urban Jr, J.F., Lunney, J.K. 2005. Up-regulation of inflammatory, regulatory and th1-immune markers in swine responding to acute toxoplasma gondii infection. Proceedings of American Association of Veterinary Parasitologists. p. 33-34.

Technical Abstract: Pigs respond quickly to infection with the intracellular parasite, Toxoplasma gondii (Tg), inducing a strong interferon-' (IFNG) dominated, T helper-1 (Th1) response. Our studies are aimed at determining the upstream regulatory factors that stimulate this response. Pigs were infected with 4.5 x 105 Tg oocysts and sacrificed at 2, 4, 7 and 14 days after infection (DAI). As early as 2 DAI Tg parasites can be found in MLN, increasing at 4-7 DAI, and clearing by 14 DAI. This correlates with changes in gene expression of innate/inflammatory, regulatory and Th1 immune markers, as determined by swine specific real-time RT-PCR assays. Peak IFNG mRNA and protein expression were observed in MLN, hepatosplenic LN (HSLN) and blood cells (PBMC) at 4-7 DAI. Statistically significant changes in IL1B, TLR2, TLR4 were observed in MLN, liver, jejunum and ileum at 4-7 DAI. Apoptotic markers were upregulated at 4-7 DAI, with liver having the greater increase starting as early as 2 DAI. IRF1, MYD88, TNF and STAT1 were statistically increased at 2 DAI in liver prior to the simultaneous upregulation of IFNG, ICSBP1, IL18 and TBX21 gene expression at 4 DAI; HLX1 increased at 7DAI. Expression of mRNA for parasite controlling factors, ARG1, NOS2A, INDO and SLC11A1 (NRAMP1), were among the largest changes found in MLN and jejunum. By flow cytometry there were no significant changes in CD3, ''T, CD4, CD8 cell subsets or activation marker expression; there were increases in CD2+/CD16+ NK cells in MLN, HSLN with infection. Overall, liver showed the most intense changes in gene expression in response to Tg infection, followed by MLN and jejunum. Up-regulation of inflammatory, regulatory and Th1-dominated markers indicates that immune mechanisms in intestinal tissues and liver are quickly activated in swine responses to control acute toxoplasmosis. Supported by ARS CRIS funds and a National Pork Board grant.