Pulmonary immune cell trafficking promotes host defense against alcohol-associated Klebsiella pneumonia

Samuelson et al show that alcohol impairs the production/processing of microbial metabolites, specifically tryptophan catabolites, resulting in immune dysregulation and impaired cellular trafficking for optimal host defense. The metabolite, indole, or probiotics making indole metabolites mitigate alcohol-induced susceptibility to Klebsiella-associated pneumonia, and that the mechanisms are partially dependent on AhR. 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.

Automated summary

Alcohol impairs immune function and cellular transport, increasing susceptibility to bacterial pneumonia. Microbial metabolites can mitigate alcohol-induced risks, partially through AhR. Microbiota therapeutics are effective in reducing the risk of alcohol-associated bacterial pneumonia.