title: Ethanol impairs mucosal immunity against Streptococcus pneumoniae infection by disrupting interleukin 17 gene expression.
abstract: Acute ethanol intoxication suppresses the host immune responses against Streptococcus pneumoniae. As interleukin 17 (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-17 receptor (IL-17R) signaling. A chronic ethanol feeding model in simian immunodeficiency virus (SIV)-infected rhesus macaques and acute ethanol intoxication in a murine model were used. Transcriptome analysis of bronchial brushes in the nonhuman 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 plus IL-1β rescued bacterial burden in the ethanol group to control levels. Taken together, the results of this study suggest 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.
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Giraldina
authors.initials: G
authors.lastname: Trevejo-Nunez
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Kong
authors.initials: K
authors.lastname: Chen
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Dufour
authors.affiliation: Department of Medicine and Department of Physiology, LSU Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Horne
authors.affiliation: Department of Medicine and Department of Physiology, LSU Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Nelson
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA jay.kolls@chp.edu.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
mesh_terms: D000818:Animals; D001980:Bronchi / Q000276:immunology; D015331:Cohort Studies; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D018928:Immunity, Mucosal / Q000187:drug effects*; D020381:Interleukin-17 / Q000096:biosynthesis*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009092:Mucous Membrane / Q000187:drug effects*; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D000431:Ethanol