tetano
Editor, Senior Moderator
Am J Respir Cell Mol Biol. 2015 Feb 18. [Epub ahead of print]
[h=1]Influenza Primes Human Lung Microvascular Endothelium to Leak upon Exposure to Staphylococcus aureus.[/h] Wang C[SUP]1[/SUP], Armstrong SM, Sugiyama MG, Tabuchi A, Krauszman A, Kuebler WM, Mullen B, Advani S, Advani A, Lee WL.
[h=3]Author information[/h]
[h=3]Abstract[/h] Rationale: The primary cause of death following influenza virus infection is lung injury due to a bacterial superinfection, yet the mechanism is unknown. Death has been attributed to virus-induced immunosuppression and bacterial overgrowth, but this hypothesis is based on data from the pre-antibiotic era and animal models that omit antimicrobial therapy. Due to diagnostic uncertainty, most patients with influenza receive antibiotics making bacterial overgrowth unlikely. Respiratory failure after superinfection presents as acute respiratory distress syndrome, a disorder characterized by lung microvascular leak and edema. Objectives: To determine whether the influenza virus sensitizes the lung endothelium to leak upon exposure to circulating bacterial-derived molecular patterns from Staphylococcus aureus. Methods: In vitro as well as in vivo models of influenza followed by Staphylococcus aureus superinfection were used. Molecular mechanisms were explored using molecular biology, knockout-mice and human autopsy specimens. Measurements and Main Results: Influenza virus infection sensitized human lung endothelium to leak when challenged with S. aureus, even at low doses of influenza and even when the pathogens were given days apart. Influenza virus increased endothelial expression of TNFR1 both in vitro and in intact lungs, a finding corroborated by human autopsy specimens of patients with influenza. Leak was recapitulated with protein A, a TNFR1-ligand, and sequential infection caused protein A-dependent loss of IκB, cleavage of caspases 8 and 3, and lung endothelial apoptosis. Mice infected sequentially with influenza virus and S. aureus developed significantly increased lung edema that was protein A- and TNFR1-dependent. Conclusions: Influenza virus primes the lung endothelium to leak, predisposing to ARDS upon exposure to S. aureus.
[h=4]KEYWORDS:[/h] Influenza; Pneumonia; Pulmonary edema; Receptors, Tumor Necrosis Factor, Type I; Superinfection
PMID: 25693001 [PubMed - as supplied by publisher]
[h=1]Influenza Primes Human Lung Microvascular Endothelium to Leak upon Exposure to Staphylococcus aureus.[/h] Wang C[SUP]1[/SUP], Armstrong SM, Sugiyama MG, Tabuchi A, Krauszman A, Kuebler WM, Mullen B, Advani S, Advani A, Lee WL.
[h=3]Author information[/h]
[h=3]Abstract[/h] Rationale: The primary cause of death following influenza virus infection is lung injury due to a bacterial superinfection, yet the mechanism is unknown. Death has been attributed to virus-induced immunosuppression and bacterial overgrowth, but this hypothesis is based on data from the pre-antibiotic era and animal models that omit antimicrobial therapy. Due to diagnostic uncertainty, most patients with influenza receive antibiotics making bacterial overgrowth unlikely. Respiratory failure after superinfection presents as acute respiratory distress syndrome, a disorder characterized by lung microvascular leak and edema. Objectives: To determine whether the influenza virus sensitizes the lung endothelium to leak upon exposure to circulating bacterial-derived molecular patterns from Staphylococcus aureus. Methods: In vitro as well as in vivo models of influenza followed by Staphylococcus aureus superinfection were used. Molecular mechanisms were explored using molecular biology, knockout-mice and human autopsy specimens. Measurements and Main Results: Influenza virus infection sensitized human lung endothelium to leak when challenged with S. aureus, even at low doses of influenza and even when the pathogens were given days apart. Influenza virus increased endothelial expression of TNFR1 both in vitro and in intact lungs, a finding corroborated by human autopsy specimens of patients with influenza. Leak was recapitulated with protein A, a TNFR1-ligand, and sequential infection caused protein A-dependent loss of IκB, cleavage of caspases 8 and 3, and lung endothelial apoptosis. Mice infected sequentially with influenza virus and S. aureus developed significantly increased lung edema that was protein A- and TNFR1-dependent. Conclusions: Influenza virus primes the lung endothelium to leak, predisposing to ARDS upon exposure to S. aureus.
[h=4]KEYWORDS:[/h] Influenza; Pneumonia; Pulmonary edema; Receptors, Tumor Necrosis Factor, Type I; Superinfection
PMID: 25693001 [PubMed - as supplied by publisher]