A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis.

A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis.
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DOI:
10.1084/jem.20090188
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发表时间:
2009-09-28
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Neyrolles O
Neyrolles O
中科院分区:
其他
文献类型:
--
作者:
Tanne A;Ma B;Boudou F;Tailleux L;Botella H;Badell E;Levillain F;Taylor ME;Drickamer K;Nigou J;Dobos KM;Puzo G;Vestweber D;Wild MK;Marcinko M;Sobieszczuk P;Stewart L;Lebus D;Gicquel B;Neyrolles O

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C型凝集素树突状细胞−特异性细胞间黏附分子-3抓取非整合素(DC-SIGN)介导微生物碳水化合物的天然免疫识别。我们通过建立缺乏DC-SIGN同源基因SIGNR1、SIGNR3和SIGNR5的小鼠株系,在体内研究了该分子在宿主对病原体反应中的功能。只有缺乏SIGNR3的动物对结核分枝杆菌的抵抗力减弱。在感染过程中,SIGNR3在肺吞噬细胞中表达,并与结核杆菌和分枝杆菌表面糖结合物相互作用,诱导关键宿主防御性炎性细胞因子的分泌,包括肿瘤坏死因子(TNF)。SIGNR3信号依赖于细胞内基于酪氨酸的基序和酪氨酸激酶Syk。因此,小鼠DC-SIGN同源物SIGNR3在保护宿主免受肺部细菌病原体侵袭方面做出了独特的贡献。
The C-type lectin dendritic cell−specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) mediates the innate immune recognition of microbial carbohydrates. We investigated the function of this molecule in the host response to pathogens in vivo, by generating mouse lines lacking the DC-SIGN homologues SIGNR1, SIGNR3, and SIGNR5. Resistance to Mycobacterium tuberculosis was impaired only in SIGNR3-deficient animals. SIGNR3 was expressed in lung phagocytes during infection, and interacted with M. tuberculosis bacilli and mycobacterial surface glycoconjugates to induce secretion of critical host defense inflammatory cytokines, including tumor necrosis factor (TNF). SIGNR3 signaling was dependent on an intracellular tyrosine-based motif and the tyrosine kinase Syk. Thus, the mouse DC-SIGN homologue SIGNR3 makes a unique contribution to protection of the host against a pulmonary bacterial pathogen.
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