The Journal of Pathology
Volume 238, Issue 1, pages 85?97, January 2016
- Kathie-Anne Walters[SUP]1[/SUP],
- Felice D'Agnillo[SUP]2[/SUP],
- Zong-Mei Sheng[SUP]4[/SUP],
- Jason Kindrachuk[SUP]3[/SUP],
- Louis M Schwartzman[SUP]4[/SUP],
- Rolf E Kuestner[SUP]1[/SUP],
- Daniel S Chertow[SUP]3,4[/SUP],
- Basil T Golding[SUP]2[/SUP],
- Jeffery K Taubenberger[SUP]4,*[/SUP] and
- John C Kash[SUP]4,*[/SUP]
Article first published online: 14 OCT 2015
1918 pandemic influenza virus and Streptococcus pneumoniae co-infection results in activation of coagulation and widespread pulmonary thrombosis in mice and humans [h=3]Abstract[/h] To study bacterial co-infection following 1918 H1N1 influenza virus infection, mice were inoculated with the 1918 influenza virus, followed by
Streptococcus pneumoniae (SP) 72 h later. Co-infected mice exhibited markedly more severe disease, shortened survival time and more severe lung pathology, including widespread thrombi. Transcriptional profiling revealed activation of coagulation only in co-infected mice, consistent with the extensive thrombogenesis observed. Immunohistochemistry showed extensive expression of tissue factor (F3) and prominent deposition of neutrophil elastase on endothelial and epithelial cells in co-infected mice. Lung sections of SP-positive 1918 autopsy cases showed extensive thrombi and prominent staining for F3 in alveolar macrophages, monocytes, neutrophils, endothelial and epithelial cells, in contrast to co-infection-positive 2009 pandemic H1N1 autopsy cases. This study reveals that a distinctive feature of 1918 influenza virus and SP co-infection in mice and humans is extensive expression of tissue factor and activation of the extrinsic coagulation pathway leading to widespread pulmonary thrombosis. Copyright ? 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
