Cutting edge:: IL-10-Independent STAT3 activation by toxoplasma gondii mediates suppression of IL-12 and TNF-α in host macrophages
Cutting edge:: IL-10-Independent STAT3 activation by toxoplasma gondii mediates suppression of IL-12 and TNF-α in host macrophages
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DOI：
10.4049/jimmunol.174.6.3148
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发表时间：
2005-03-15
影响因子：
4.4
通讯作者：
Denkers, EY
中科院分区：
文献类型：
--
作者：
Butcher, BA;Kim, L;Denkers, EY
刚地弓形虫感染小鼠巨噬细胞使细胞抵抗LPS触发的促炎作用。在这项研究中，我们发现细胞侵袭伴随着宿主STAT3的快速和持续激活。可溶性刚地弓形虫提取物或热杀死的速殖子没有激活STAT3，这表明它需要活的寄生虫。寄生虫诱导的STAT3磷酸化和lps触发的tnf - α和IL-12的抑制在il -10缺失的巨噬细胞中是完整的，排除了这种抗炎细胞因子在弓形虫抑制作用中的作用。最重要的是，弓形虫不能有效抑制lps触发的stat3缺陷巨噬细胞中tnf - α和IL-12的合成。这些结果表明，弓形虫利用宿主STAT3来阻止LPS触发的IL-12和tnf - α的产生，首次揭示了弓形虫抑制巨噬细胞促炎细胞因子产生的分子机制。
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-alpha 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-alpha 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-alpha production, revealing for the first time a molecular mechanism underlying the parasite's suppressive effect on macrophage proinflammatory cytokine production.