Ethanol impairs mucosal immunity against Streptococcus pneumoniae infection by disrupting interleukin 17 gene expression

Infect Immun. 2015 May;83(5):2082-8. doi: 10.1128/IAI.02869-14. Epub 2015 Mar 9.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchi / immunology
  • Cohort Studies
  • Disease Models, Animal
  • Ethanol / toxicity*
  • Gene Expression / drug effects*
  • Gene Expression Profiling
  • Immunity, Mucosal / drug effects*
  • Interleukin-17 / biosynthesis*
  • Macaca mulatta
  • Male
  • Mice
  • Mucous Membrane / drug effects*
  • Pneumococcal Infections / immunology*
  • Streptococcus pneumoniae / immunology*


  • Interleukin-17
  • Ethanol