Malachowa Natalia, Freedman Brett, Sturdevant Daniel E, Kobayashi Scott D, Nair Vinod, Feldmann Friederike, Starr Tregei, Steele-Mortimer Olivia, Kash John C, Taubenberger Jeffery K, Feldmann Heinz, DeLeo Frank R
Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Genomics Unit, Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
mSphere. 2018 Jan 3;3(1). doi: 10.1128/mSphereDirect.00567-17. eCollection 2018 Jan-Feb.
Neutrophils are essential cells of host innate immunity. Although the role of neutrophils in defense against bacterial and fungal infections is well characterized, there is a relative paucity of information about their role against viral infections. Influenza A virus (IAV) infection can be associated with secondary bacterial coinfection, and it has long been posited that the ability of IAV to alter normal neutrophil function predisposes individuals to secondary bacterial infections. To better understand this phenomenon, we evaluated the interaction of pandemic or seasonal H1N1 IAV with human neutrophils isolated from healthy persons. These viruses were ingested by human neutrophils and elicited changes in neutrophil gene expression that are consistent with an interferon-mediated immune response. The viability of neutrophils following coculture with either pandemic or seasonal H1N1 IAV was similar for up to 18 h of culture. Notably, neutrophil exposure to seasonal (but not pandemic) IAV primed these leukocytes for enhanced functions, including production of reactive oxygen species and bactericidal activity. Taken together, our results are at variance with the universal idea that IAV impairs neutrophil function directly to predispose individuals to secondary bacterial infections. Rather, we suggest that some strains of IAV prime neutrophils for enhanced bacterial clearance. A long-standing notion is that IAV inhibits normal neutrophil function and thereby predisposes individuals to secondary bacterial infections. Here we report that seasonal H1N1 IAV primes human neutrophils for enhanced killing of . Moreover, we provide a comprehensive view of the changes in neutrophil gene expression during interaction with seasonal or pandemic IAV and report how these changes relate to functions such as bactericidal activity. This study expands our knowledge of IAV interactions with human neutrophils.
中性粒细胞是宿主固有免疫的重要细胞。虽然中性粒细胞在抵御细菌和真菌感染中的作用已得到充分阐明，但关于它们在抵抗病毒感染中的作用的信息相对较少。甲型流感病毒（IAV）感染可能与继发性细菌合并感染有关，长期以来人们一直认为IAV改变正常中性粒细胞功能的能力使个体易患继发性细菌感染。为了更好地理解这一现象，我们评估了大流行或季节性H1N1 IAV与从健康人分离的人类中性粒细胞之间的相互作用。这些病毒被人类中性粒细胞摄取，并引发了与干扰素介导的免疫反应一致的中性粒细胞基因表达变化。与大流行或季节性H1N1 IAV共培养后，中性粒细胞的活力在长达18小时的培养过程中相似。值得注意的是，中性粒细胞暴露于季节性（而非大流行）IAV会使这些白细胞的功能增强，包括活性氧的产生和杀菌活性。综上所述，我们的结果与IAV直接损害中性粒细胞功能从而使个体易患继发性细菌感染这一普遍观点不一致。相反，我们认为某些IAV毒株会使中性粒细胞做好增强细菌清除的准备。一个长期存在的观点是，IAV会抑制正常中性粒细胞功能，从而使个体易患继发性细菌感染。在这里我们报告，季节性H1N1 IAV会使人类中性粒细胞做好增强杀灭……的准备。此外，我们全面了解了中性粒细胞在与季节性或大流行IAV相互作用期间基因表达的变化，并报告了这些变化与杀菌活性等功能的关系。这项研究扩展了我们对IAV与人类中性粒细胞相互作用的认识。
