Pulmonary immune cell trafficking promotes host defense against alcohol-associated Klebsiella pneumonia.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
23 08 2021
23 08 2021
Historique:
received:
20
04
2020
accepted:
05
08
2021
entrez:
24
8
2021
pubmed:
25
8
2021
medline:
15
12
2021
Statut:
epublish
Résumé
The intestinal microbiota generates many different metabolites which are critical for the regulation of host signaling pathways. In fact, a wide-range of diseases are associated with increased levels of local or systemic microbe-derived metabolites. In contrast, certain bacterial metabolites, such as tryptophan metabolites, are known to contribute to both local and systemic homeostasis. Chronic alcohol consumption is accompanied by alterations to intestinal microbial communities, and their functional capacities. However, little is known about the role of alcohol-associated dysbiosis on host defense against bacterial pneumonia. Our previous work using fecal transplantation demonstrated that alcohol-associated intestinal dysbiosis, independent of ethanol consumption, increased susceptibility to Klebsiella pneumonia. Here, we demonstrate that intestinal microbiota treatments mitigate the increased risk of alcohol-associated pneumonia. Treatment with the microbial metabolite indole or with probiotics reduced pulmonary and extrapulmonary bacterial burden, restored immune responses, and improved cellular trafficking required for host defense. Protective effects were, in part, mediated by aryl hydrocarbon receptors (AhR), as inhibition of AhR diminished the protective effects. Thus, alcohol appears to impair the production/processing of tryptophan catabolites resulting in immune dysregulation and impaired cellular trafficking. These data support microbiota therapeutics as novel strategies to mitigate the increased risk for alcohol-associated bacterial pneumonia.
Identifiants
pubmed: 34426641
doi: 10.1038/s42003-021-02524-0
pii: 10.1038/s42003-021-02524-0
pmc: PMC8382828
doi:
Substances chimiques
Indoles
0
Ethanol
3K9958V90M
indole
8724FJW4M5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
997Subventions
Organisme : NIAAA NIH HHS
ID : P60 AA009803
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA027199
Pays : United States
Organisme : NIAAA NIH HHS
ID : K99 AA026336
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM104940
Pays : United States
Organisme : NIAAA NIH HHS
ID : P50 AA009803
Pays : United States
Organisme : NIAAA NIH HHS
ID : UH2 AA026226
Pays : United States
Organisme : NIAAA NIH HHS
ID : R00 AA026336
Pays : United States
Informations de copyright
© 2021. The Author(s).
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