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CUTTING EDGE |
in Host Macrophages1
* Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, Department of Immunology;
University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; and
Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105
Infection of mouse macrophages by Toxoplasma gondii renders the cells resistant to proinflammatory effects of LPS triggering. In this study, we show that cell invasion is accompanied by rapid and sustained activation of host STAT3. Activation of STAT3 did not occur with soluble T. gondii extracts or heat-killed tachyzoites, demonstrating a requirement for live parasites. Parasite-induced STAT3 phosphorylation and suppression of LPS-triggered TNF-
and IL-12 was intact in IL-10-deficient macrophages, ruling out a role for this anti-inflammatory cytokine in the suppressive effects of T. gondii. Most importantly, Toxoplasma could not effectively suppress LPS-triggered TNF- and IL-12 synthesis in STAT3-deficient macrophages. These results demonstrate that T. gondii exploits host STAT3 to prevent LPS-triggered IL-12 and TNF- production, revealing for the first time a molecular mechanism underlying the parasite’s suppressive effect on macrophage proinflammatory cytokine production.
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