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. 2015 Jun;185(6):1528–1536. doi: 10.1016/j.ajpath.2014.08.030

Figure 3.

Figure 3

Relationship between pathological changes and host responses during severe primary influenza and secondary bacterial infections in human autopsies and experimental animal infections. Necrotizing tracheitis (1) in a 2009 pandemic H1N1 fatality.51Inset shows the relative expression of inflammatory and type I interferon (IFN) gene expression responses in fatal 1918 influenza infection compared to seasonal virus in cynomolgus macaques.58 Severe necrotizing bronchitis/bronchiolitis (2) in a 1918 influenza autopsy sample showing intense viral antigen staining in the ciliated and goblet cells of the respiratory epithelium, but not in basal cells.50Inset shows the relative expression of inflammatory response and cell death genes in lungs of mice infected with 1918 compared to seasonal H1N1.58 Secondary bacterial pneumonias (3) with massive infiltration of neutrophils into alveolar airspaces in a 1918 pandemic influenza13 fatal case (right panel). Left panel: Gram stain showing presence of Streptococcus pneumoniae bacteria (arrows) on remaining basal epithelial cells (nuclei labeled BC) and a macrophage (M) in mouse lung after coinfection of 2009 pandemic H1N1 and S. pneumoniae.72Inset shows loss of lung repair and regeneration gene expression responses in mice infected with 2009 pandemic H1N1 with a secondary S. pneumoniae infection compared to primary 2009 pandemic H1N1 infection.66 Development of diffuse alveolar damage (DAD) (4) with alveolar hyaline membrane formation, varying degrees of acute intra-alveolar edema, acute hemorrhage, interstitial and airspace inflammatory infiltrates, and small-vessel thromboses in 1918 pandemic influenza (top panel)6,9,51 and 2009 pandemic influenza (bottom panel)51 autopsies, along with pronounced alveolar epithelial immunostaining for reactive oxygen species (ROS) damage in mouse tissue infected with 1918 influenza virus.66Inset shows relative expression of inflammatory and ROS response genes in lungs of mice infected with 1918 compared to seasonal H1N1.66 Photomicrograph in 1 was modified from Gill et al (published by National Academy of Sciences of the United States of America)51; in 2 from Sheng et al (published by College of American Pathologists)50; in 3 from Morens et al (published by Oxford University Press)13 (right panel) and Kash et al (published by American Society for Microbiology)72 (left panel); and in 4 from Taubenberger and Morens (published by Annual Reviews)6 (top panel), Kash et al (published by Elsevier B.V.)66 (middle panel), and Gill et al (published by National Academy of Sciences of the United States of America)51 (bottom panel). All images used with permission of the publishers.