Toxoplasma gondii Inhibits Covalent Modification of Histone H3 at the IL-10 Promoter in Infected Macrophages

PLoS One. 2009 Oct 27;4(10):e7589.

Toxoplasma gondii Inhibits Covalent Modification of Histone H3 at the IL-10 Promoter in Infected Macrophages

Leng J, Denkers EY.

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.

Infection of macrophages with the protozoan parasite Toxoplasma gondii results in inhibition of a large panel of LPS-responsive cytokines, including TNF-alpha, while leaving others such as IL-10 intact. Recent studies provide evidence that the parasite interferes with chromatin remodeling at the TNF-alpha promoter that is normally associated with LPS stimulation, but that is not required for TLR4 induction of IL-10. Here, we examined the effect of Toxoplasma on IL-10 induced by simultaneous signaling through TLR4 and FcgammaR, a combined stimulus that triggers histone H3 covalent modification at the IL-10 promoter resulting in high level IL-10 cytokine production. We show that the parasite inhibits high level IL-10 production and prevents histone H3 Ser(10) phosphorylation and Lys(9/14) acetylation at the IL-10 promoter. These results provide compelling evidence that T. gondii targets the host cell chromatin remodeling machinery to down-regulate cytokine responses in infected macrophages.

PMID: 19859561 [PubMed - as supplied by publisher]