Journal
MUCOSAL IMMUNOLOGY
Volume 12, Issue 2, Pages 518-530Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/s41385-018-0106-4
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Funding
- NIH [HL127805, HL115618, AI117229, HL119682]
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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. INT and CCR2(-/-) mice were infected with 100 plaque forming units (pfu) H1N1 intranasally alone or were challenged on day 5 with 7 x 10(7) 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.
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