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As interleukin 17 (IL-17) is a critical cytokine in host defense against extracellular pathogens, including<jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>, 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-1\u03b2 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<jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>.<\/jats:p>","DOI":"10.1128\/iai.02869-14","type":"journal-article","created":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T01:52:45Z","timestamp":1425952365000},"page":"2082-2088","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Ethanol Impairs Mucosal Immunity against Streptococcus pneumoniae Infection by Disrupting Interleukin 17 Gene Expression"],"prefix":"10.1128","volume":"83","author":[{"given":"Giraldina","family":"Trevejo-Nunez","sequence":"first","affiliation":[{"name":"Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kong","family":"Chen","sequence":"additional","affiliation":[{"name":"Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason P.","family":"Dufour","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory J.","family":"Bagby","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Physiology, LSU Health Sciences Center, New Orleans, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William T.","family":"Horne","sequence":"additional","affiliation":[{"name":"Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Physiology, LSU Health Sciences Center, New Orleans, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay K.","family":"Kolls","sequence":"additional","affiliation":[{"name":"Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.1.3.447"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/1.3.425"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2011.06.045"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1081902"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158298"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36731"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000159"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2013.07.022"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.4049\/jimmunol.162.4.2347","article-title":"Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways","volume":"162","author":"Laan M","year":"1999","unstructured":"Laan M, Cui ZH, Hoshino H, Lotvall J, Sjostrand M, Gruenert DC, Skoogh BE, Linden A. 1999. 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