Resident Vdelta1+ gammadelta T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production.
Resident Vdelta1+ gammadelta T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production.
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DOI：
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发表时间：
2007
影响因子：
4.4
通讯作者：
K. Shibata;H. Yamada;H. Hara;K. Kishihara;Y. Yoshikai
中科院分区：
文献类型：
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作者：
K. Shibata;H. Yamada;H. Hara;K. Kishihara;Y. Yoshikai
中性粒细胞浸润感染部位，在宿主防御中发挥关键作用，特别是对抗细胞外细菌。在本研究中，我们发现了一个快速和短暂的生产IL-17后，腹膜内感染大肠杆菌，前流入的中性粒细胞。IL-17的中和导致中性粒细胞浸润减少和细菌清除受损。离体细胞内细胞因子流式细胞术分析显示，γ δ T细胞群是IL-17的主要来源。通过mAb处理耗尽γ δ T细胞的小鼠或遗传上缺乏Vdelta 1的小鼠在E. coli感染，表明V δ 1（+）γ δ T细胞作为IL-17来源的重要性。进一步揭示了幼稚小鼠腹腔中的γ δ T细胞响应于IL-23而产生IL-17，IL-23在E.大肠杆菌感染的TLR 4信号依赖的方式。因此，尽管γ δ T细胞通常被认为是早期诱导的免疫应答的一部分，其桥接先天性和适应性免疫应答，但我们的研究证明了γ δ T细胞作为控制嗜中性粒细胞介导的先天性免疫应答的宿主防御的第一道防线的新作用。
Neutrophils infiltrate the site of infection and play critical roles in host defense, especially against extracellular bacteria. In the present study, we found a rapid and transient production of IL-17 after i.p. infection with Escherichia coli, preceding the influx of neutrophils. Neutralization of IL-17 resulted in a reduced infiltration of neutrophils and an impaired bacterial clearance. Ex vivo intracellular cytokine flow cytometric analysis revealed that gammadelta T cell population was the major source of IL-17. Mice depleted of gammadelta T cells by mAb treatment or mice genetically lacking Vdelta1 showed diminished IL-17 production and reduced neutrophil infiltration after E. coli infection, indicating an importance of Vdelta1(+) gammadelta T cells as the source of IL-17. It was further revealed that gammadelta T cells in the peritoneal cavity of naive mice produced IL-17 in response to IL-23, which was induced rapidly after E. coli infection in a TLR4 signaling-dependent manner. Thus, although gammadelta T cells are generally regarded as a part of early induced immune responses, which bridge innate and adaptive immune responses, our study demonstrated a novel role of gammadelta T cells as a first line of host defense controlling neutrophil-mediated innate immune responses.