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- Title
Toxoplasma gondii Inhibits Covalent Modification of Histone H3 at the IL-10 Promoter in Infected Macrophages.
- Authors
Jin Leng; Denkers, Eric Y.
- Abstract
Infection of macrophages with the protozoan parasite Toxoplasma gondii results in inhibition of a large panel of LPSresponsive cytokines, including TNF-α, while leaving others such as IL-10 intact. Recent studies provide evidence that the parasite interferes with chromatin remodeling at the TNF-α 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 FcγR, 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 Ser10 phosphorylation and Lys9/14 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.
- Subjects
MACROPHAGES; PROTOZOAN diseases; PARASITES; TOXOPLASMA gondii; CYTOKINES; HISTONES; ACETYLATION; CELLS; CHROMATIN
- Publication
PLoS ONE, 2009, Vol 4, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0007589