Innate, antigen‐independent role for T cells in the activation of the immune system by Propionibacterium acnes
Innate, antigen‐independent role for T cells in the activation of the immune system by Propionibacterium acnes
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T 细胞在痤疮丙酸杆菌激活免疫系统中发挥先天的、不依赖于抗原的作用
DOI：
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发表时间：
2010
影响因子：
5.4
通讯作者：
M. Freudenberg
中科院分区：
文献类型：
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作者：
Sandrine Y. Tchaptchet;J. Kirberg;N. Freudenberg;W. Schamel;C. Galanos;M. Freudenberg
痤疮丙酸杆菌是一种常见的致病菌，但也是一种机会致病菌。在小鼠中，痤疮丙酸杆菌发挥强大的免疫调节活性，包括形成肝内肉芽肿和诱导LPS超敏反应。这些活性依赖于通过TLR 9识别痤疮丙酸杆菌和随后的IL-12介导的IFN-γ产生。我们发现，痤疮丙酸杆菌可诱导巨噬细胞中IL-12 p40和p35 mRNA的表达，以及肝脏CD 4 + T细胞和NK细胞中IFN-γ mRNA的表达。在用痤疮丙酸杆菌引发后，CD 4 + T细胞作为主要的IFN-γ mRNA来源。在不存在CD 4 + T细胞的情况下，CD 8 + T细胞（无论抗原特异性如何）或NK细胞可以产生足够的IFN-γ以诱导痤疮丙酸杆菌驱动的免疫效应。此外，在αβT细胞不存在的情况下，γδT细胞还能够产生对LPS和肝内肉芽肿形成的强烈增强的TNF-α和IFN-γ应答。因此，在微生物的压力下，不同类型的T细胞，独立于其抗原特异性，发挥NK细胞样功能，这对先天免疫系统的激活起决定性作用。
Propionibacterium acnes is a human commensal but also an opportunistic pathogen. In mice, P. acnes exerts strong immunomodulatory activities, including formation of intrahepatic granulomas and induction of LPS hypersensitivity. These activities are dependent on P. acnes recognition via TLR9 and subsequent IL‐12‐mediated IFN‐γ production. We show that P. acnes elicits IL‐12p40 and p35 mRNA expression in macrophages, and IFN‐γ mRNA in liver CD4+ T cells and NK cells. After priming with P. acnes, CD4+ T cells serve as the major IFN‐γ mRNA source. In the absence of CD4+ T cells, CD8+ T cells (regardless of antigenic specificity) or NK cells can produce sufficient IFN‐γ to induce the P. acnes‐driven immune effects. Moreover, in the absence of αβT cells, γδT cells also enable the development of strongly enhanced TNF‐α and IFN‐γ responses to LPS and intrahepatic granuloma formation. Thus, under microbial pressure, different T‐cell types, independent of their antigen specificity, exert NK‐cell‐like functions, which contribute decisively to the activation of the innate immune system.