Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium.
Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium.
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DOI：
10.1371/journal.pone.0147064
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hizawa N
中科院分区：
文献类型：
--
作者：
Matsuyama M;Ishii Y;Sakurai H;Ano S;Morishima Y;Yoh K;Takahashi S;Ogawa K;Hizawa N
鸟分枝杆菌复合体（MAC）是人类非结核分枝杆菌病最常见的病因。Th 17免疫在细胞内细菌（如MAC）的发病机制中的作用目前尚不清楚。转录因子RAR相关孤儿受体γ t（RORγt）被认为是Th 17细胞发育的主要调节因子。在此，我们研究了RORγt在宿主抗MAC感染反应中的作用。野生型（WT）小鼠和RORγ t过表达小鼠通过肠道接种感染MAC。WT小鼠和RORγ t过表达小鼠的全身MAC生长没有差异。然而，与WT小鼠相比，MAC感染后RORγ t过表达小鼠的嗜酸性肺部炎症增强。MAC感染后，RORγ t过表达小鼠的肺中细胞因子表达向Th 17表型转变;这些小鼠肺中IL-6和IL-17的水平显著高于WT小鼠。除了IL-17单阳性T细胞增加外，MAC感染后RORγ t过表达小鼠肺中产生IL-17和干扰素-γ的T细胞也升高。这些结果表明，RORγt过表达介导的Th 17偏倚通过调节MAC感染期间中性粒细胞募集到感染部位而促进局部炎症而不是全身反应。
Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial disease in humans. The role of Th17 immunity in the pathogenesis of intracellular bacteria, such as MAC, is not currently understood. Transcription factor RAR-related orphan receptor gamma t (RORγt) is known as the master regulator for Th17 cell development. Here, we investigated the role of RORγt in host responses against MAC infection. Wild-type (WT) mice and RORγt-overexpressing mice were infected with MAC via intratracheal inoculation. Systemic MAC growth was not different between WT mice and RORγt-overexpressing mice. However, neutrophilic pulmonary inflammation following MAC infection was enhanced in RORγt-overexpressing mice compared with that in WT mice. The cytokine expression shifted toward a Th17 phenotype in the lungs of RORγt-overexpressing mice following MAC infection; the levels of IL-6 and IL-17 were significantly higher in the lung of these mice than in WT mice. In addition to the increase in IL-17 single-positive T cells, T cells producing both IL-17 and interferon-γ were elevated in the lung of RORγt-overexpressing mice following MAC infection. These findings suggest that RORγt overexpression-mediated Th17 bias contributes to local inflammation rather than systemic responses, by regulating neutrophil recruitment into the sites of infection during MAC infection.