Toxoplasma gondii inhibits covalent modification of histone H3 at the IL-10 promoter in infected macrophages.
Toxoplasma gondii inhibits covalent modification of histone H3 at the IL-10 promoter in infected macrophages.
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DOI：
10.1371/journal.pone.0007589
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发表时间：
2009-10-27
期刊：
影响因子：
3.7
通讯作者：
Denkers EY
中科院分区：
文献类型：
--
作者：
Leng J;Denkers EY
用原生动物寄生虫弓形虫感染巨噬细胞会抑制大量LPS反应性细胞因子，包括TNF-α，而其他细胞因子（如IL-10）则保持不变。最近的研究提供了证据表明，寄生虫干扰TNF-α启动子处的染色质重塑，这通常与LPS刺激相关，但不是TLR 4诱导IL-10所必需的。在此，我们检测了弓形虫对通过TLR 4和FcγR同时信号传导诱导的IL-10的影响，这是一种联合刺激，可触发IL-10启动子处的组蛋白H3共价修饰，导致高水平IL-10细胞因子产生。我们发现，寄生虫抑制高水平的IL-10的生产，并阻止组蛋白H3 Ser 10磷酸化和Lys 9/14乙酰化的IL-10启动子。这些结果为T.弓形虫靶向宿主细胞染色质重塑机制，以下调感染的巨噬细胞中的细胞因子应答。
Infection of macrophages with the protozoan parasite Toxoplasma gondii results in inhibition of a large panel of LPS-responsive 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.