Bridging of host-microbiota tryptophan partitioning by the serotonin pathway in fungal pneumonia

Bridging of host-microbiota tryptophan partitioning by the serotonin pathway in fungal pneumonia

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Abstract The aromatic amino acid L-tryptophan (Trp) is essentially metabolized along the host and microbial pathways.While much is known about the role played by downstream metabolites turbo air m3f72-3-n of each pathways in intestinal homeostasis, their role in lung immune homeostasis is underappreciated.Here we have examined the role played by the Trp hydroxylase/5-hydroxytryptamine (5-HT) pathway in calibrating host and microbial Trp metabolism during Aspergillus fumigatus pneumonia.We found that 5-HT produced by mast cells essentially contributed to pathogen clearance and immune homeostasis radio birdman tshirt in infection by promoting the host protective indoleamine-2,3-dioxygenase 1/kynurenine pathway and limiting the microbial activation of the indole/aryl hydrocarbon receptor pathway.This occurred via regulation of lung and intestinal microbiota and signaling pathways.

5-HT was deficient in the sputa of patients with Cystic fibrosis, while 5-HT supplementation restored the dysregulated Trp partitioning in murine disease.These findings suggest that 5-HT, by bridging host-microbiota Trp partitioning, may have clinical effects beyond its mood regulatory function in respiratory pathologies with an inflammatory component.