tetano
Editor, Senior Moderator
EMBO Rep. 2015 Aug 11. pii: e201540473. [Epub ahead of print]
[h=1]TRAIL+ monocytes and monocyte-related cells cause lung damage and thereby increase susceptibility to influenza-Streptococcus pneumoniae coinfection.[/h] Ellis GT[SUP]1[/SUP], Davidson S[SUP]1[/SUP], Crotta S[SUP]1[/SUP], Branzk N[SUP]1[/SUP], Papayannopoulos V[SUP]1[/SUP], Wack A[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Streptococcus pneumoniae coinfection is a major cause of influenza-associated mortality; however, the mechanisms underlying pathogenesis or protection remain unclear. Using a clinically relevant mouse model, we identify immune-mediated damage early during coinfection as a new mechanism causing susceptibility. Coinfected CCR2[SUP]-/-[/SUP] mice lacking monocytes and monocyte-derived cells control bacterial invasion better, show reduced epithelial damage and are overall more resistant than wild-type controls. In influenza-infected wild-type lungs, monocytes and monocyte-derived cells are the major cell populations expressing the apoptosis-inducing ligand TRAIL. Accordingly, anti-TRAIL treatment reduces bacterial load and protects against coinfection if administered during viral infection, but not following bacterial exposure. Post-influenza bacterial outgrowth induces a strong proinflammatory cytokine response and massive inflammatory cell infiltrate. Depletion of neutrophils or blockade of TNF-α facilitate bacterial outgrowth, leading to increased mortality, demonstrating that these factors aid bacterial control. We conclude that inflammatory monocytes recruited early, during the viral phase of coinfection, induce TRAIL-mediated lung damage, which facilitates bacterial invasion, while TNF-α and neutrophil responses help control subsequent bacterial outgrowth. We thus identify novel determinants of protection versus pathology in influenza-Streptococcus pneumoniae coinfection.
? 2015 Francis Crick Institute Published under the terms of the CC BY 4.0 license.
[h=4]KEYWORDS:[/h] Streptococcus pneumoniae ; C‐C‐chemokine receptor type (CCR) 2; TNF‐related apoptosis‐inducing ligand (TRAIL); influenza; neutrophil
PMID: 26265006 [PubMed - as supplied by publisher] Free full text
[h=1]TRAIL+ monocytes and monocyte-related cells cause lung damage and thereby increase susceptibility to influenza-Streptococcus pneumoniae coinfection.[/h] Ellis GT[SUP]1[/SUP], Davidson S[SUP]1[/SUP], Crotta S[SUP]1[/SUP], Branzk N[SUP]1[/SUP], Papayannopoulos V[SUP]1[/SUP], Wack A[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Streptococcus pneumoniae coinfection is a major cause of influenza-associated mortality; however, the mechanisms underlying pathogenesis or protection remain unclear. Using a clinically relevant mouse model, we identify immune-mediated damage early during coinfection as a new mechanism causing susceptibility. Coinfected CCR2[SUP]-/-[/SUP] mice lacking monocytes and monocyte-derived cells control bacterial invasion better, show reduced epithelial damage and are overall more resistant than wild-type controls. In influenza-infected wild-type lungs, monocytes and monocyte-derived cells are the major cell populations expressing the apoptosis-inducing ligand TRAIL. Accordingly, anti-TRAIL treatment reduces bacterial load and protects against coinfection if administered during viral infection, but not following bacterial exposure. Post-influenza bacterial outgrowth induces a strong proinflammatory cytokine response and massive inflammatory cell infiltrate. Depletion of neutrophils or blockade of TNF-α facilitate bacterial outgrowth, leading to increased mortality, demonstrating that these factors aid bacterial control. We conclude that inflammatory monocytes recruited early, during the viral phase of coinfection, induce TRAIL-mediated lung damage, which facilitates bacterial invasion, while TNF-α and neutrophil responses help control subsequent bacterial outgrowth. We thus identify novel determinants of protection versus pathology in influenza-Streptococcus pneumoniae coinfection.
? 2015 Francis Crick Institute Published under the terms of the CC BY 4.0 license.
[h=4]KEYWORDS:[/h] Streptococcus pneumoniae ; C‐C‐chemokine receptor type (CCR) 2; TNF‐related apoptosis‐inducing ligand (TRAIL); influenza; neutrophil
PMID: 26265006 [PubMed - as supplied by publisher] Free full text