Shibata Kensuke, Yamada Hisakata, Hara Hiromitsu, Kishihara Kenji, Yoshikai Yasunobu
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
J Immunol. 2007 Apr 1;178(7):4466-72. doi: 10.4049/jimmunol.178.7.4466.
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.
中性粒细胞浸润感染部位，在宿主防御中发挥关键作用，尤其是针对细胞外细菌。在本研究中，我们发现腹腔注射大肠杆菌感染后，在中性粒细胞流入之前，白细胞介素-17（IL-17）会快速短暂产生。中和IL-17会导致中性粒细胞浸润减少和细菌清除受损。体外细胞内细胞因子流式细胞术分析显示，γδT细胞群体是IL-17的主要来源。通过单克隆抗体处理耗尽γδT细胞的小鼠或基因上缺乏Vδ1的小鼠，在大肠杆菌感染后IL-17产生减少且中性粒细胞浸润减少，表明Vδ1(+)γδT细胞作为IL-17来源的重要性。进一步研究发现，未感染小鼠腹腔中的γδT细胞在白细胞介素-23（IL-23）刺激下产生IL-17，而IL-23在大肠杆菌感染后以Toll样受体4（TLR4）信号依赖的方式迅速诱导产生。因此，尽管γδT细胞通常被视为早期诱导免疫反应的一部分，连接先天性和适应性免疫反应，但我们的研究证明了γδT细胞作为宿主防御的第一线，控制中性粒细胞介导的先天性免疫反应的新作用。
