Infiltration of inflammatory macrophages and neutrophils and widespread pyroptosis in lung drive influenza lethality in nonhuman primates
Fig 1
Lethal H5N1 influenza is associated with activation of antiviral and inflammatory pathways in lung.
(A) Infectious virus titer in three different regions of left and right lung at necropsy from the six macaques. The day post infection of sacrifice is noted for each animal. (B) Hematoxylin and eosin staining of lungs from an uninfected macaque and infected macaque 133 at day 2 post infection, and in situ hybridization of influenza RNA in lung of macaque 133 at day 2 post infection. Dotted lines outline airways and highlight intense cellular infiltration in airways. Asterisks, arrowhead, and arrow mark alveolar consolidation, hemorrhage, and cellular infiltration in lung parenchyma, respectively. (C) Volcano plot of differentially expressed genes in lungs of uninfected and lethally infected macaques. Genes to the left of the Y-axis are decreased in lethal influenza relative to uninfected macaques, whereas genes to the right are increased in lethal influenza relative to uninfected macaques. (D) Bar graph showing enrichment false discovery rate (FDR) for the select biological pathways of differentially expressed genes in uninfected and infected lung. Pathways enriched in lethal influenza are shown above the X-axis, whereas pathways downregulated in lethal influenza are below X-axis. See also S1 and S2 Tables for a full list of up-and downregulated pathways.