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

Infection and Immunity
Giraldina Trevejo-NunezJay K Kolls

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.

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Citations

Jan 5, 2016·Trends in Biotechnology·Andrew B HillCharles H Jones
Apr 6, 2017·Immunology and Cell Biology·Brian T CampfieldJay K Kolls
Jul 20, 2018·Alcoholism, Clinical and Experimental Research·Feifei GuoYulia A Nevzorova
May 14, 2019·Alcoholism, Clinical and Experimental Research·Wendy A NeveuViranuj Sueblinvong
Jul 24, 2020·ELife·Nathalia Luisa Sousa de Oliveira MalaccoFrederico Marianetti Soriani
Apr 15, 2018·Alcohol·Holly J HulsebusElizabeth J Kovacs
Apr 26, 2021·Molecular Immunology·Julien LemaitrePauline Maisonnasse

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