TLR9 signaling is essential for the innate NK cell response in murine cutaneous leishmaniasis
TLR9 signaling is essential for the innate NK cell response in murine cutaneous leishmaniasis
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DOI：
10.1002/eji.200737182
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发表时间：
2007-12-01
影响因子：
5.4
通讯作者：
Bogdan, Christian
中科院分区：
文献类型：
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作者：
Liese, Jan;Schleicher, Ulrike;Bogdan, Christian
TLR衔接分子MyD 88缺陷的小鼠死于利什曼原虫（L.）少校然而，有助于控制这种细胞内寄生虫的TLR仍有待确定。在此，我们发现TLR 9是完整的L.主要寄生虫或L.主要的DNA和早期IFN-γ表达和NK细胞的细胞毒性后，感染L.主要是在体内。在感染的急性期，TLR 9（-/-）小鼠表现出比C57 BL/6野生型对照更严重的皮肤病变和更高的寄生虫负荷。尽管TLR 9缺陷导致感染部位和引流淋巴结中IL-4、IL-13和iNOS 1 mRNA的瞬时增加和iNOS的表达减少，但它并不阻止Th 1细胞的发育和感染的最终消退。我们的结论是，TLR 9信号是必要的NK细胞的活化，但保护性T细胞对L。主要是在体内。
Mice deficient for the TLR adaptor molecule MyD88 succumb to a local infection with Leishmania (L.) major. However, the TLR(s) that contribute to the control of this intracellular parasite remain to be defined. Here, we show that TLR9 was required for the induction of IL-12 in bone marrow-derived DC by intact L. major parasites or L. major DNA and for the early IFN-gamma expression and cytotoxicity of NK cells following infection with L. major in vivo. During the acute phase of infection TLR9(-/-) mice exhibited more severe skin lesions and higher parasite burdens than C57BL/6 wild-type controls. Although TLR9 deficiency led to a transient increase of IL-4, IL-13 and arginase 1 mRNA and a reduced expression of iNOS at the site of infection and in the draining lymph nodes, it did not prevent the development of Th1 cells and the ultimate resolution of the infection. We conclude that TLR9 signaling is essential for NK cell activation, but dispensable for a protective T cell response to L. major in vivo.