Kinetics of systemic cytokine and brain chemokine expression in murine Toxoplasma infection

J Parasitol. 2008 Apr 10:1. [Epub ahead of print]

Kinetics of systemic cytokine and brain chemokine expression in murine Toxoplasma infection

Aviles HO, Stiles J, O P, Orshal J, Leid J, Sonnenfeld G, Monroy FP.

Toxoplasma gondii often migrates to the central nervous system in immunocompromised patients where it induces a severe inflammation referred as Toxoplasma encephalitis. The mechanisms involved in control of parasite multiplication and prevention of Toxoplasma encephalitis remain unclear. The objective of this study was to characterize the inflammatory response in the brain of mice during acute T. gondii infection with emphasis in the expression of chemokine receptors. Susceptible C57BL/6 mice were orally infected with 10 cysts of the low virulent ME49 strain of T. gondii. Levels of cytokines (TNF-alpha, IFN-gamma, IL-10, IL-6 and IL-12p70) and chemokines (CCL/2MCP-1) were measured in plasma at 5, 10, 15, 20, and 30 days after infection. In addition, the mRNA expression of chemokines (CCL5/RANTES, CCL2/MCP-1, CCL4/MIP-1beta) and chemokine receptors (CCR1, CCR2, CCR5, CCR7, CCR8, CXCR4 and CXR5) were measured in brain tissues at the same time points. Plasma levels of IFN-gamma and CCL2/MCP-1 were highly expressed at day 5, while TNF-alpha had a moderate increase at day 5, peaking at day 10 and returning to normal levels by day 30. Plasma levels of IL-10, IL-6, and IL-12p70 were not detected throughout the study. Analyses of mRNA expression of chemokines and chemokine receptors in the brain showed that CCL5/RANTES, CCR7, CXCR4 and CXCR5 were up-regulated, peaking after 10 days of T. gondii infection. Similar pattern of expression was observed for anti-tachyzoite IgG and IgM antibodies. Our results suggest that T. gondii infection is controlled at local and systemic levels and that pro-inflammatory proteins and their receptors may be acting coordinately to induce stage conversion and prevent parasite multiplication and development of Toxoplasma encephalitis. The early production of IFN-gamma and the delayed expression of CXCR4 and CXCR5 indicate that T. gondii induces an early robust cellular immune response followed by a strong and sustained antibody mediated immunity.

PMID: 18576716 [PubMed - as supplied by publisher]