Announcement

Collapse
No announcement yet.

CCR2 mediates increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • CCR2 mediates increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17

    Mucosal Immunol. 2018 Nov 29. doi: 10.1038/s41385-018-0106-4. [Epub ahead of print]
    CCR2 mediates increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17.

    Gurczynski SJ1, Nathani N1, Warheit-Niemi HI2, Hult EM2, Podsiad A1, Deng J1,3, Zemans RL1, Bhan U1,4, Moore BB5,6.
    Author information

    Abstract

    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-/- mice were infected with 100 plaque forming units (pfu) H1N1 intranasally alone or were challenged on day 5 with 7 ? 107 colony forming units (cfu) methicillin-resistant Staphylococcus aureus intratracheally. WT mice express abundant CCL2 mRNA and protein post-H1N1 alone or dual infection. CCR2-/- 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-/- mice following sequential infection as compared to WT mice, which was also associated with significantly greater accumulation of CD103+ DC. Finally, WT mice treated with a CCR2 inhibitor showed improved bacterial clearance in association with similar cytokine profiles as CCR2-/- 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
Working...
X