1918 pandemic influenza virus and Streptococcus pneumoniae co-infection results in activation of coagulation and widespread pulmonary thrombosis in mice and humans

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, in...

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Bibliographic Details
Published in:The Journal of pathology 2016-01, Vol.238 (1), p.85-97
Main Authors: Walters, Kathie-Anne, D'Agnillo, Felice, Sheng, Zong-Mei, Kindrachuk, Jason, Schwartzman, Louis M, Kuestner, Rolf E, Chertow, Daniel S, Golding, Basil T, Taubenberger, Jeffery K, Kash, John C
Format: Article
Language:English
Subjects:
1918 influenza
Animals
Blood Coagulation
co-infection
Coinfection - complications
Disease Models, Animal
extrinsic pathway of coagulation
Female
Humans
Immunohistochemistry
inflammation
Influenza A Virus, H1N1 Subtype
Influenza Pandemic, 1918-1919
Influenza virus
Influenza, Human - complications
Influenza, Human - microbiology
Influenza, Human - pathology
Mice
Mice, Inbred BALB C
Oligonucleotide Array Sequence Analysis
Orthomyxoviridae Infections - complications
Orthomyxoviridae Infections - microbiology
Orthomyxoviridae Infections - pathology
Pneumococcal Infections - complications
Pneumococcal Infections - microbiology
Pneumococcal Infections - pathology
Pulmonary Embolism - microbiology
Pulmonary Embolism - pathology
pulmonary thrombosis
Reverse Transcriptase Polymerase Chain Reaction
Streptococcus pneumoniae
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Summary: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.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.4638