Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils

• DOI: 10.1128/jvi.00817-15
• Publication Date: 2015-06-11T07:28:11Z
• Authors: Jeremy V. Camp; Ulas Bagci; Yong-Kyu Chu; Brendan Squier; Mostafa Fraig; Silvia M. Uriarte; Haixun Guo; Daniel J. Mollura; Colleen B. Jonsson
• Keywords: Respiratory tract; Infiltration (HVAC); Interleukin 8

ABSTRACT Infection of the lower respiratory tract by influenza A viruses results in increases inflammation and immune cell infiltration lung. The dynamic relationships among lung microenvironments, lung, systemic host responses during infection remain poorly understood. Here we used extensive systematic histological analysis coupled with live imaging to gain access these ferrets infected 2009 H1N1 pandemic virus (H1N1pdm virus). Neutrophil levels rose lungs H1N1pdm virus-infected 6 h postinfection became concentrated at areas bronchiolar epithelium 1 day (dpi). In addition, neutrophil were increased throughout alveolar spaces first 3 dpi returned baseline dpi. Histochemical staining revealed that occurred two waves, dpi, gene expression within microenvironments suggested types neutrophils. Specifically, CCL3 levels, but not CXCL8/interleukin 8 (IL-8) higher discrete coincided neutrophils into We monitor over time [ 18 F]fluorodeoxyglucose (FDG). Sites ferret high FDG uptake had proliferative epithelium. summary, invaded globally focally sites infection. Increased did correlate uptake; hence, may reflect prior have experienced damage, as evidenced bronchial regeneration tissues levels. IMPORTANCE Severe disease is characterized an acute airways progress rapidly organ failure death. Well-developed animal models mimic human are essential understanding complex microenvironment, organ, system controlling replication, inflammation, progression. Employing model infection, comprehensive analyses address specific hypotheses regarding spatial temporal occur progression inflammation. show general invasion level (lung) also a distinct pattern localized accumulation microenvironment site Moreover, biphasic Finally, early sustained metabolic response damage repair lungs.