Neutrophils regulate the lung inflammatory response via γδ T cell infiltration in an experimental mouse model of human metapneumovirus infection
Neutrophils regulate the lung inflammatory response via γδ T cell infiltration in an experimental mouse model of human metapneumovirus infection
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DOI：
10.1189/jlb.4a1216-519rr
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发表时间：
2017-06-01
影响因子：
5.5
通讯作者：
Guerrero-Plata, Antonieta
中科院分区：
文献类型：
--
作者：
Cheemarla, Nagarjuna R.;Del Rocio Banos-Lara, Ma;Guerrero-Plata, Antonieta
中性粒细胞是人体循环中最丰富的白细胞。它们是第一个被招募到感染部位的免疫细胞群。然而，中性粒细胞在呼吸道病毒感染中调节宿主免疫反应的作用在很大程度上是未知的。为了阐明中性粒细胞在呼吸道抗病毒防御中的作用，我们使用了人偏肺病毒（HMPV）感染的实验小鼠模型。HMPV是副粘病毒科的一个成员，是一种主要的呼吸道病原体，在年轻、老年和免疫功能低下的患者中引起严重症状，如细支气管炎和肺炎。我们证明，嗜中性粒细胞是HMPV感染后招募到肺部的免疫细胞的主要群体。这使我们假设嗜中性粒细胞是HMPV感染期间免疫应答的关键参与者，从而调节HMPV诱导的肺发病机制。与HMPV感染的有能力的小鼠相比，使用mAb在体内特异性消耗中性粒细胞并同时感染HMPV表现出更高水平的炎性细胞因子、肺部炎症和严重的临床疾病。有趣的是，中性粒细胞的缺乏改变了γ δ T细胞在肺中的积累。在HMPV感染期间，γ δ T细胞的缺乏导致肺部炎症减少。这些新的发现表明，中性粒细胞通过调节γ δ T细胞浸润到感染部位，在控制HMPV诱导的炎症反应中发挥关键作用。
Neutrophils are the most abundant leukocytes in human circulation. They are the first immune cell population recruited to the sites of infection. However, the role of neutrophils to regulate host immune responses during respiratory viral infections is largely unknown. To elucidate the role of neutrophils in respiratory antiviral defense, we used an experimental mouse model of human metapneumovirus (HMPV) infection. HMPV, a member of the Paramyxoviridae family, is a leading respiratory pathogen causing severe symptoms, such as bronchiolitis and pneumonia, in young, elderly, and immunocompromised patients. We demonstrate that neutrophils are the predominant population of immune cells recruited into the lungs after HMPV infection. This led us to hypothesize that neutrophils represent a key player of the immune response during HMPV infection, thereby regulating HMPV-induced lung pathogenesis. Specific depletion of neutrophils in vivo using a mAb and simultaneous infection with HMPV exhibited higher levels of inflammatory cytokines, pulmonary inflammation, and severe clinical disease compared with HMPV-infected, competent mice. Interestingly, the lack of neutrophils altered gamma delta T cell accumulation in the lung. The absence of gamma delta T cells during HMPV infection led to reduced pulmonary inflammation. These novel findings demonstrate that neutrophils play a critical role in controlling HMPV-induced inflammatory responses by regulating gamma delta T cell infiltration to the site of infection.