Lower respiratory tract infection of the ferret by 2009 H1N1 pandemic influenza A virus triggers biphasic, systemic, and local recruitment of neutrophils

Jeremy V. Camp, Ulas Bagci, Yong Kyu Chu, Brendan Squier, Mostafa Fraig, Silvia M. Uriarte, Haixun Guo, Daniel J. Mollura, Colleen Jonsson

Research output: Contribution to journalArticle

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Abstract

Infection of the lower respiratory tract by influenza A viruses results in increases in inflammation and immune cell infiltration in the lung. The dynamic relationships among the lung microenvironments, the lung, and systemic host responses during infection remain poorly understood. Here we used extensive systematic histological analysis coupled with live imaging to gain access to these relationships in ferrets infected with the 2009 H1N1 pandemic influenza A virus (H1N1pdm virus). Neutrophil levels rose in the lungs of H1N1pdm virus-infected ferrets 6 h postinfection and became concentrated at areas of the H1N1pdm virusinfected bronchiolar epithelium by 1 day postinfection (dpi). In addition, neutrophil levels were increased throughout the alveolar spaces during the first 3 dpi and returned to baseline by 6 dpi. Histochemical staining revealed that neutrophil infiltration in the lungs occurred in two waves, at 1 and 3 dpi, and gene expression within microenvironments suggested two types of neutrophils. Specifically, CCL3 levels, but not CXCL8/interleukin 8 (IL-8) levels, were higher within discrete lung microenvironments and coincided with increased infiltration of neutrophils into the lung. We used live imaging of ferrets to monitor host responses within the lung over time with [18F]fluorodeoxyglucose (FDG). Sites in the H1N1pdm virus-infected ferret lung with high FDG uptake had high levels of proliferative epithelium. In summary, neutrophils invaded the H1N1pdm virus-infected ferret lung globally and focally at sites of infection. Increased neutrophil levels in microenvironments did not correlate with increased FDG uptake; hence, FDG uptake may reflect prior infection and inflammation of lungs that have experienced damage, as evidenced by bronchial regeneration of tissues in the lungs at sites with high FDG levels.

Original languageEnglish (US)
Pages (from-to)8733-8748
Number of pages16
JournalJournal of Virology
Volume89
Issue number17
DOIs
StatePublished - Jan 1 2015

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Ferrets
Neutrophil Infiltration
ferrets
Influenza A virus
Pandemics
pandemic
Respiratory Tract Infections
respiratory tract diseases
neutrophils
lungs
Lung
Neutrophils
infection
Epithelium
Infection
epithelium
inflammation
image analysis
Fluorodeoxyglucose F18
interleukin-8

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Lower respiratory tract infection of the ferret by 2009 H1N1 pandemic influenza A virus triggers biphasic, systemic, and local recruitment of neutrophils. / Camp, Jeremy V.; Bagci, Ulas; Chu, Yong Kyu; Squier, Brendan; Fraig, Mostafa; Uriarte, Silvia M.; Guo, Haixun; Mollura, Daniel J.; Jonsson, Colleen.

In: Journal of Virology, Vol. 89, No. 17, 01.01.2015, p. 8733-8748.

Research output: Contribution to journalArticle

Camp, Jeremy V. ; Bagci, Ulas ; Chu, Yong Kyu ; Squier, Brendan ; Fraig, Mostafa ; Uriarte, Silvia M. ; Guo, Haixun ; Mollura, Daniel J. ; Jonsson, Colleen. / Lower respiratory tract infection of the ferret by 2009 H1N1 pandemic influenza A virus triggers biphasic, systemic, and local recruitment of neutrophils. In: Journal of Virology. 2015 ; Vol. 89, No. 17. pp. 8733-8748.
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AU - Uriarte, Silvia M.

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