Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
Infect Immun. 2020 May 20;88(6). doi: 10.1128/IAI.00171-20.
is an opportunistic pathogen that causes chronic and life-threatening infections in immunocompromised patients. A better understanding of the role that innate immunity plays in the control of infection is crucial for therapeutic development. Specifically, the role of unconventional immune cells like γδ T cells in the clearance of lung infection is not yet well characterized. In this study, the role of γδ T cells was examined in an acute mouse model of lung infection. In the absence of γδ T cells, mice displayed impaired bacterial clearance and decreased survival, outcomes which were associated with delayed neutrophil recruitment and impaired recruitment of other immune cells (macrophages, T cells, natural killer cells, and natural killer T [NKT] cells) into the airways. Despite reduced NKT cell recruitment in the airways of mice lacking γδ T cells, NKT cell-deficient mice exhibited wild-type level control of infection. Proinflammatory cytokines were also altered in γδ T cell-deficient mice, with increased production of interleukin-1β, interleukin-6, and tumor necrosis factor. γδ T cells did not appear to contribute significantly to the production of interleukin-17A or the chemokines CXCL1 and CXCL2. Importantly, host survival could be improved by inhibiting tumor necrosis factor signaling with the soluble receptor construct etanercept in γδ cell-deficient mice. These findings demonstrate that γδ T cells play a protective role in coordinating the host response to lung infection, both in contributing to early immune cell recruitment and by limiting inflammation.
是一种机会性病原体，可导致免疫功能低下患者发生慢性和危及生命的感染。更好地了解固有免疫在控制感染中的作用对于治疗开发至关重要。具体来说，γδ T 细胞等非常规免疫细胞在清除肺部感染中的作用尚未得到很好的描述。在本研究中，研究人员在急性小鼠肺部感染模型中检查了 γδ T 细胞的作用。在没有 γδ T 细胞的情况下，小鼠显示出细菌清除能力受损和存活率降低的情况，这与中性粒细胞募集延迟以及其他免疫细胞（巨噬细胞、T 细胞、自然杀伤细胞和自然杀伤 T [NKT]细胞）向气道募集受损有关。尽管缺乏 γδ T 细胞的小鼠气道中 NKT 细胞募集减少，但 NKT 细胞缺陷型小鼠对感染的控制仍具有野生型水平。γδ T 细胞缺陷型小鼠中的促炎细胞因子也发生改变，白细胞介素-1β、白细胞介素-6 和肿瘤坏死因子的产生增加。γδ T 细胞似乎对白细胞介素-17A 或趋化因子 CXCL1 和 CXCL2 的产生没有显著贡献。重要的是，通过在 γδ 细胞缺陷型小鼠中使用可溶性受体构建物依那西普抑制肿瘤坏死因子信号，可以改善宿主存活。这些发现表明，γδ T 细胞在协调宿主对肺部感染的反应中发挥保护作用，既有助于早期免疫细胞募集，又限制炎症。
