Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States.
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore.
Front Cell Infect Microbiol. 2019 Apr 16;9:108. doi: 10.3389/fcimb.2019.00108. eCollection 2019.
Exaggerated host innate immune responses have been implicated in severe influenza pneumonia. We have previously demonstrated that excessive neutrophils recruited during influenza infection drive pulmonary pathology through induction of neutrophil extracellular traps (NETs) and release of extracellular histones. Chemokine receptors (CRs) are essential in the recruitment and activation of leukocytes. Although neutrophils have been implicated in influenza pathogenesis, little is known about their phenotypic changes, including expression of CRs occurring in the infected -lung microenvironment. Here, we examined CC and CXC CRs detection in circulating as well as lung-recruited neutrophils during influenza infection in mice using flow cytometry analyses. Our studies revealed that lung-recruited neutrophils displayed induction of CRs, including CCR1, CCR2, CCR3, CCR5, CXCR1, CXCR3, and CXCR4, all of which were marginally induced in circulating neutrophils. CXCR2 was the most predominant CR observed in both circulating and lung-infiltrated neutrophils after infection. The stimulation of these induced CRs modulated neutrophil phagocytic activity, ligand-specific neutrophil migration, bacterial killing, and NETs induction . These findings indicate that neutrophils induce a novel CR repertoire in the infectious lung microenvironment, which alters their functionality during influenza pneumonia.
宿主先天免疫反应过度与严重流感肺炎有关。我们之前的研究表明，流感感染期间过度募集的中性粒细胞通过诱导中性粒细胞胞外诱捕网（NETs）和细胞外组蛋白的释放，导致肺部病理学改变。趋化因子受体（CRs）在白细胞的募集和激活中是必不可少的。虽然中性粒细胞已被认为与流感发病机制有关，但对于它们在感染肺部微环境中发生的表型变化，包括 CRs 的表达，知之甚少。在这里，我们使用流式细胞术分析检查了流感感染期间循环和肺募集中性粒细胞中 CC 和 CXC CRs 的检测。我们的研究表明，肺募集的中性粒细胞显示出 CRs 的诱导，包括 CCR1、CCR2、CCR3、CCR5、CXCR1、CXCR3 和 CXCR4，所有这些在循环中性粒细胞中都有轻微诱导。感染后，CXCR2 是循环和肺浸润中性粒细胞中最主要的 CR。这些诱导的 CR 的刺激调节中性粒细胞的吞噬活性、配体特异性中性粒细胞迁移、杀菌和 NETs 诱导。这些发现表明，中性粒细胞在感染性肺部微环境中诱导新的 CR 谱，改变了它们在流感肺炎期间的功能。
