tetano
Editor, Senior Moderator
Mucosal Immunol. 2018 Nov 29. doi: 10.1038/s41385-018-0106-4. [Epub ahead of print]
[h=1]CCR2 mediates increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17.[/h] Gurczynski SJ[SUP]1[/SUP], Nathani N[SUP]1[/SUP], Warheit-Niemi HI[SUP]2[/SUP], Hult EM[SUP]2[/SUP], Podsiad A[SUP]1[/SUP], Deng J[SUP]1,[/SUP][SUP]3[/SUP], Zemans RL[SUP]1[/SUP], Bhan U[SUP]1,[/SUP][SUP]4[/SUP], Moore BB[SUP]5,[/SUP][SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Post influenza bacterial pneumonia is associated with significant mortality and morbidity. Dendritic cells (DCs) play a crucial role in host defense against bacterial pneumonia, but their contribution to post influenza-susceptibility to secondary bacterial pneumonia is incompletely understood. WT and CCR2[SUP]-/-[/SUP] mice were infected with 100 plaque forming units (pfu) H1N1 intranasally alone or were challenged on day 5 with 7 ? 10[SUP]7[/SUP] colony forming units (cfu) methicillin-resistant Staphylococcus aureus intratracheally. WT mice express abundant CCL2 mRNA and protein post-H1N1 alone or dual infection. CCR2[SUP]-/-[/SUP] mice had significantly higher survival as compared to WT mice, associated with significantly improved bacterial clearance at 24 and 48 h (10-fold and 14-fold, respectively) post bacterial challenge. There was robust upregulation of IL-23 and IL-17 as well as downregulation of IL-27 expression in CCR2[SUP]-/-[/SUP] mice following sequential infection as compared to WT mice, which was also associated with significantly greater accumulation of CD103[SUP]+[/SUP] DC. Finally, WT mice treated with a CCR2 inhibitor showed improved bacterial clearance in association with similar cytokine profiles as CCR2[SUP]-/-[/SUP] mice. Thus, CCR2 significantly contributes to increased susceptibility to bacterial infection after influenza pneumonia likely via altered dendritic cell responses and thus, CCR2 antagonism represents a potential therapeutic strategy.
PMID: 30498200 DOI: 10.1038/s41385-018-0106-4
[h=1]CCR2 mediates increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17.[/h] Gurczynski SJ[SUP]1[/SUP], Nathani N[SUP]1[/SUP], Warheit-Niemi HI[SUP]2[/SUP], Hult EM[SUP]2[/SUP], Podsiad A[SUP]1[/SUP], Deng J[SUP]1,[/SUP][SUP]3[/SUP], Zemans RL[SUP]1[/SUP], Bhan U[SUP]1,[/SUP][SUP]4[/SUP], Moore BB[SUP]5,[/SUP][SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Post influenza bacterial pneumonia is associated with significant mortality and morbidity. Dendritic cells (DCs) play a crucial role in host defense against bacterial pneumonia, but their contribution to post influenza-susceptibility to secondary bacterial pneumonia is incompletely understood. WT and CCR2[SUP]-/-[/SUP] mice were infected with 100 plaque forming units (pfu) H1N1 intranasally alone or were challenged on day 5 with 7 ? 10[SUP]7[/SUP] colony forming units (cfu) methicillin-resistant Staphylococcus aureus intratracheally. WT mice express abundant CCL2 mRNA and protein post-H1N1 alone or dual infection. CCR2[SUP]-/-[/SUP] mice had significantly higher survival as compared to WT mice, associated with significantly improved bacterial clearance at 24 and 48 h (10-fold and 14-fold, respectively) post bacterial challenge. There was robust upregulation of IL-23 and IL-17 as well as downregulation of IL-27 expression in CCR2[SUP]-/-[/SUP] mice following sequential infection as compared to WT mice, which was also associated with significantly greater accumulation of CD103[SUP]+[/SUP] DC. Finally, WT mice treated with a CCR2 inhibitor showed improved bacterial clearance in association with similar cytokine profiles as CCR2[SUP]-/-[/SUP] mice. Thus, CCR2 significantly contributes to increased susceptibility to bacterial infection after influenza pneumonia likely via altered dendritic cell responses and thus, CCR2 antagonism represents a potential therapeutic strategy.
PMID: 30498200 DOI: 10.1038/s41385-018-0106-4