Submitted to: International Journal for Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/24/2001
Publication Date: 10/20/2001
Citation: Solano Aguilar, G., Beshah, E., Vengroski, K.G., Zarlenga, D.S., Jauregui, L., Cosio, M., Douglass, L.W., Dubey, J.P., Lunney, J.K. 2001. Cytokine and lymphocyte profile in miniature swine after oral infection with toxoplasma gondii oocysts. International Journal for Parasitology. vol. 31, pp. 187-95. Interpretive Summary: Toxoplasmosis, a protozoan parasite infection, causes abortion in livestock, mental retardation, loss of vision in children, and deaths in immunocompromised individuals. How swine become infected in nature is not fully known, but it is clear that T. gondii oocysts shed in cat feces play an important role as direct contaminants of pig feed and water. Despite the extensive literature on immunity to T. gondii in mice and humans, little is known of swine immune responses to this infection. Antibody titers have been reported for swine but these are highly variable and, as with other species, not predictive of effective immunity. The specific objective of this study was to define the immune response to T. gondii infection. A group of 66 piglets of different swine leukocyte antigen (SLA) haplotypes were evaluated for a period of 6 weeks after oral infection with T. gondii oocysts. Cells subsets from peripheral blood were characterized by comparing the change in phenotype, using a broad panel of monoclonal antibodies (mAb) that identify the most important swine B and T cell subsets. Cytokine expression for IFN-g, IL-10, IL-12 and IL-12R was quantified by RT-PCR comparing its expression at different times after the infection. Parasite burden was assessed in tongue by bioassay in cats and brain tissues from all pigs after necropsy by bioassay in mice to determine whether genetically resistant pigs can be identified. Patterns of temporal decreases in CD4+cells, and increases in CD8+ and double CD4/CD8+ cells in peripheral blood indicated an early induction of T helper cell activity following inoculation with oocysts. Pigs responded to T. gondii infection by simultaneously inducing proinflammatory cytokines (IFN-g) early and anti-inflammatory cytokines (IL-10) later for controlling parasite growth.
Technical Abstract: Pigs are considered as an important source of Toxoplasma gondii infection for humans. A major strategy for immune prophylaxis of toxoplasmosis in swine is the understanding of the immune response against T.gondii infection. The phenotype of peripheral blood mononuclear cells (PBMC) and the kinetics of interferon gamma (IFN-g), interleukin 12 (IL-12) and interleukin 10 (IL-10) transcriptional changes were characterized in miniature swine following infection. A total of 66, 4 to 9 month old miniature swine were used for three experiments performed during a period of two years. All pigs were fed » 1000 oocysts of the VEG strain of T.gondii. Blood samples were obtained from the pigs on the day of inoculation and at days 3,6,10,17,25,32 and 40 after the infection. An increase in expression of activation markers CD25 and SLA-DQ was detected in the first week of the infection and a significant increase in the percentage of CD8+ cells of PBMC were observed in the second week of the infection. Competitive RT-PCR indicated an increase in IFN-g mRNA as well as a reduction in IL-10 mRNA during the second week post infection. Increase in IL-12 transcription was not observed until the fourth week of the infection. Overall, the ability of pigs to respond to T. gondii infection by simultaneously inducing pro inflammatory cytokines early and anti inflammatory cytokines after is likely an indication of the requirement to strike a balance between controlling parasite growth and avoiding cytokine toxicity.