TLR9 is required for the gut-associated lymphoid tissue response following oral infection of Toxoplasma gondii
TLR9 is required for the gut-associated lymphoid tissue response following oral infection of Toxoplasma gondii
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DOI：
10.4049/jimmunol.176.12.7589
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发表时间：
2006-06-15
影响因子：
4.4
通讯作者：
Kasper, Lloyd H.
中科院分区：
文献类型：
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作者：
Minns, Laurie A.;Menard, Laurence C.;Kasper, Lloyd H.
由多种细胞（包括上皮细胞、B细胞和树突细胞）表达的TLR是用各种微生物产物刺激后免疫应答的重要引发剂。一些TLR需要衔接蛋白MyD 88，其是弓形虫感染后免疫应答的重要介质。以前，TLR 9介导的先天免疫应答主要与未甲基化的细菌CpG DNA的连接相关。在这项研究中，我们发现TLR 9是口腔感染T细胞后引发的Th 1型炎症反应所必需的。刚地。经口感染T.弓形虫易感野生型（WT; C57 BL/6）而非TLR 9（-/-）（B6背景）小鼠发生Th 1依赖性急性致死性回肠炎; TLR 9（-/-）小鼠比对照WT小鼠具有更高的寄生虫负荷，与。抑制IFN-γ依赖的寄生虫杀伤。在TLR 9（-/-）寄生虫感染小鼠的固有层中观察到总T细胞和产生IFN-γ的T细胞频率的减少。通过来自WT小鼠中感染肠的细胞观察到TLR 9和I型IFN产生。树突状细胞群的TLR 9表达对于它们在感染小鼠的肠系膜淋巴结中的扩增是必需的。感染嵌合小鼠删除TLR 9的造血或非造血区室证明TLR 9表达的细胞从两个区室是重要的有效的T细胞应答口腔感染。这些观察结果表明，TLR 9介导对口腔寄生虫感染的先天性应答，并参与有效的Th 1型免疫应答的发展。
TLRs expressed by a variety of cells, including epithelial cells, B cells, and dendritic cells, are important initiators of the immune response following stimulation with various microbial products. Several of the TLRs require the adaptor protein, MyD88, which is an important mediator for the immune response following Toxoplasma gondii infection. Previously, TLR9-mediated innate immune responses were predominantly associated with ligation of unmethylated bacterial CpG DNA. In this study, we show that TLR9 is required for the Th1-type inflammatory response that ensues following oral infection with T. gondii. After oral infection with T. gondii, susceptible wild-type (WT; C57BL/6) but not TLR9(-/-) (B6 background) mice develop a Th1-dependent acute lethal ileitis; TLR9(-/-) mice have higher parasite burdens than control WT mice, consistent with. depressed IFN-gamma-dependent parasite killing. A reduction in the total T cell and IFN-gamma-producing T cell frequencies was observed in the lamina propria of the TLR9(-/-) parasite-infected mice. TLR9 and type I IFN production was observed by cells from infected intestines in WT mice. TLR9 expression by dendritic cell populations is essential for their expansion in the mesenteric lymph nodes of infected mice. Infection of chimeric mice deleted of TLR9 in either the hemopoietic or nonhemopoietic compartments demonstrated that TLR9 expression by cells from both compartments is important for efficient T cell responses to oral infection. These observations demonstrate that TLR9 mediates the innate response to oral parasite infection and is involved in the development of an effective Th1-type immune response.