Infect Immun. 2015 Mar 9. pii: IAI.02869-14. [Epub ahead of print]
Ethanol Impairs Mucosal Immunity Against Streptococcus pneumoniae Infection by Disrupting IL-17 Gene Expression.
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Abstract
Acute ethanol intoxication suppresses the host immune responses against Streptococcus pneumoniae. As IL-17 is a critical cytokine in host defense against extracellular pathogens including S. pneumoniae, we hypothesized that ethanol impairs mucosal immunity against this pathogen by disrupting IL-17 production or IL-17R signaling. A chronic ethanol feeding model in SIV-infected Rhesus macaques and acute ethanol in a murine model were used. Transcriptome analysis of bronchial brushes in the non-human primate model showed downregulation of the expression of IL-17 regulated chemokines in ethanol fed animals, a finding also replicated in the murine model. Surprisingly, recombinant CXCL1 and CXCL5 but not IL-17 or IL-23 + IL1β rescued bacterial burden in the ethanol group to control levels. Taken together, this study suggests that ethanol impairs IL-17 mediated chemokine production in the lung. Thus, exogenous luminal restoration of IL-17 related chemokines, CXCL1 and CXCL5, improves host defenses against S. pneumoniae.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25754201 [PubMed - as supplied by publisher]
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