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Influenza Suppresses Neutrophil Recruitment to the Lung and Exacerbates Secondary Invasive Pulmonary Aspergillosis
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-10 , DOI: 10.4049/jimmunol.2000067
Joshua M Tobin 1 , Kara L Nickolich 1 , Krishnaveni Ramanan 1 , Matthew J Pilewski 1 , Kristina D Lamens 2 , John F Alcorn 3 , Keven M Robinson 4
Affiliation  

Key Points Postinfluenza IPA can be effectively modeled in mice. Neutrophil recruitment to the lung is decreased in postinfluenza IPA. STAT1 signaling increases susceptibility to postinfluenza IPA. Aspergillus fumigatus is an environmental fungus that can cause invasive pulmonary aspergillosis when spores are inhaled into the respiratory tract and invade airway or lung tissue. Influenza is a common respiratory virus that can cause severe respiratory disease, and postinfluenza invasive pulmonary aspergillosis, which is becoming a well-recognized clinical problem, typically occurs in critically ill patients. Mice challenged with influenza A PR/8/34 H1N1 and subsequently challenged with A. fumigatus had increased fungal burden, viral burden, inflammation, and mortality compared with single infected mice. Neutrophil recruitment in the lung of superinfected mice was decreased; however, mice were not neutropenic, and there was no difference in absolute blood neutrophils between groups. Additionally, CXCL1 and CXCL2 were decreased in lungs of superinfected mice compared with controls. IFN levels were increased in mice that received influenza, and deletion of STAT1 resulted in decreased fungal burden, increased airway and lung neutrophils, and increased CXCL1 compared with wild-type mice, whereas deletion of STAT2 did not change fungal burden or airway neutrophilia compared with wild-type mice. These data demonstrate a mechanism by which influenza A–induced STAT1 signaling inhibits neutrophil recruitment and increases susceptibility to postinfluenza invasive pulmonary aspergillosis.

中文翻译:

流感抑制中性粒细胞向肺的募集并加剧继发性侵袭性肺曲霉病

关键点 流感后 IPA 可以在小鼠中有效建模。在流感后 IPA 中,中性粒细胞向肺的募集减少。STAT1 信号增加了对流感后 IPA 的易感性。烟曲霉是一种环境真菌,当孢子吸入呼吸道并侵入气道或肺组织时,可引起侵袭性肺曲霉病。流感是一种常见的呼吸道病毒,可引起严重的呼吸道疾病,流感后侵袭性肺曲霉病正在成为公认的临床问题,通常发生在重症患者身上。与单一感染小鼠相比,接受甲型流感 PR/8/34 H1N1 攻击并随后接受烟曲霉攻击的小鼠的真菌负担、病毒负担、炎症和死亡率均有所增加。重复感染小鼠肺中的中性粒细胞募集减少;然而,小鼠没有中性粒细胞减少,并且各组之间的绝对血液中性粒细胞没有差异。此外,与对照相比,重复感染小鼠肺中的 CXCL1 和 CXCL2 减少。与野生型小鼠相比,接受流感的小鼠的 IFN 水平增加,STAT1 的缺失导致真菌负担减少,气道和肺中性粒细胞增加,CXCL1 增加,而与野生型小鼠相比,STAT2 的缺失并未改变真菌负担或气道中性粒细胞增多。野生型小鼠。这些数据证明了甲型流感诱导的 STAT1 信号抑制中性粒细胞募集并增加对流感后侵袭性肺曲霉病的易感性的机制。并且两组之间的绝对血中性粒细胞没有差异。此外,与对照相比,重复感染小鼠肺中的 CXCL1 和 CXCL2 减少。与野生型小鼠相比,接受流感的小鼠的 IFN 水平增加,STAT1 的缺失导致真菌负担减少,气道和肺中性粒细胞增加,CXCL1 增加,而与野生型小鼠相比,STAT2 的缺失并未改变真菌负担或气道中性粒细胞增多。野生型小鼠。这些数据证明了甲型流感诱导的 STAT1 信号抑制中性粒细胞募集并增加对流感后侵袭性肺曲霉病的易感性的机制。并且两组之间的绝对血中性粒细胞没有差异。此外,与对照相比,重复感染小鼠肺中的 CXCL1 和 CXCL2 减少。与野生型小鼠相比,接受流感的小鼠的 IFN 水平增加,STAT1 的缺失导致真菌负担减少,气道和肺中性粒细胞增加,CXCL1 增加,而与野生型小鼠相比,STAT2 的缺失并未改变真菌负担或气道中性粒细胞增多。野生型小鼠。这些数据证明了甲型流感诱导的 STAT1 信号抑制中性粒细胞募集并增加对流感后侵袭性肺曲霉病的易感性的机制。与野生型小鼠相比,接受流感的小鼠的 IFN 水平增加,STAT1 的缺失导致真菌负担减少,气道和肺中性粒细胞增加,CXCL1 增加,而与野生型小鼠相比,STAT2 的缺失并未改变真菌负担或气道中性粒细胞增多。野生型小鼠。这些数据证明了甲型流感诱导的 STAT1 信号抑制中性粒细胞募集并增加对流感后侵袭性肺曲霉病的易感性的机制。与野生型小鼠相比,接受流感的小鼠的 IFN 水平增加,STAT1 的缺失导致真菌负担减少,气道和肺中性粒细胞增加,CXCL1 增加,而与野生型小鼠相比,STAT2 的缺失并未改变真菌负担或气道中性粒细胞增多。野生型小鼠。这些数据证明了甲型流感诱导的 STAT1 信号抑制中性粒细胞募集并增加对流感后侵袭性肺曲霉病的易感性的机制。
更新日期:2020-06-10
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