New journal publication in Journal of Virology
J.V. Camp, U. Bagci, Y. Chu, B. Squier, M. Fraig, S.M. Uriarte, H. Guo, D.J. Mollura, C.B. Jonsson,
Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic Systemic and Local Neutrophil Recruitment
Journal of Virology, in press, 2015.
Infection of the lower respiratory tract by influenza A viruses (IAV) results in an increase in inflammation and immune cell infiltration in the lung. The dynamic relationships of early IAV-host responses within microenvironments of the lung, the lung and systemic responses remain poorly understood. Herein, we used an extensive systematic histologic analysis coupled with live imaging to gain access to these relationships within the lungs of ferrets infected with 2009 pandemic IAV H1N1 (H1N1pdm). IAV distribution, neutrophil accumulation and selected immune gene expression profiles were measured within lung microenvironments. We show that increased gene expression of CCL3, but not CXCL8/IL-8, in discrete areas of H1N1pdm-infection coincided with increased infiltration of neutrophils in the lungs. We use histochemical staining to show that neutrophils infiltrated the lungs in two waves, at 1 and 3 days post-infection (dpi). Comprehensive, unbiased histologic analyses of the caudal lung lobes reinforced these findings, showing that neutrophil levels rose in the lungs of H1N1pdm-infected ferrets as early as 6 hours post-infection relative to mock-infected controls, and became highly concentrated at areas of H1N1pdm-infected bronchiolar epithelium by 1 dpi. In addition, neutrophils were increased throughout the alveolar spaces relative to mock-infected animals during the first 3 dpi. By 6 dpi, lung regeneration was detected by the presence of proliferating epithelial cells and neutrophil levels returned to mock-infected baseline levels. Live imaging of H1N1pdm-infected ferrets with radiolabeled fluorodeoxyglucose did not correlate neutrophil density after H1N1pdm infection, but with bronchial regeneration within the ferret thoracic cavity.