Vibrio cholerae high cell density quorum sensing activates the host intestinal innate immune response

• Published in: Cell reports (Cambridge) 2022-09, Vol.40 (12), p.111368-111368, Article 111368
• Main Authors: Jugder, Bat-Erdene, Batista, Juliana H., Gibson, Jacob A., Cunningham, Paul M., Asara, John M., Watnick, Paula I.
• Format: Article
• Language: English
• Subjects: antimicrobial peptide; Bacterial Proteins - metabolism; Cell Count; Cholera Toxin; Drosophila melanogaster intestine; Gene Expression Regulation, Bacterial; Humans; immune deficiency pathway; Immunity, Innate; infection; innate immunity; Intestines; Polysaccharides - metabolism; posterior midgut; Quorum Sensing; serotonin; Serotonin - metabolism; Tryptophan - metabolism; Vibrio cholerae; Vibrio cholerae - metabolism; Virulence Factors - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.111368

Quorum sensing fundamentally alters the interaction of Vibrio cholerae with aquatic environments, environmental hosts, and the human intestine. At high cell density, the quorum-sensing regulator HapR represses not only expression of cholera toxin and the toxin co-regulated pilus, virulence factors essential in human infection, but also synthesis of the Vibrio polysaccharide (VPS) exopolysaccharide-based matrix required for abiotic and biotic surface attachment. Here, we describe a feature of V. cholerae quorum sensing that shifts the host-pathogen interaction toward commensalism. By repressing pathogen consumptive anabolic metabolism and, in particular, tryptophan uptake, V. cholerae HapR stimulates host intestinal serotonin production. This, in turn, activates host intestinal innate immune signaling to promote host survival. [Display omitted] •V. cholerae HapR represses pathogen tryptophan consumption•Host enterocytes convert dietary tryptophan to serotonin•Intestinal serotonin synthesis activates IMD signaling and prolongs host survival•HapR orchestrates a commensal interaction between host and pathogen Here, Jugder et al. show that the V. cholerae master high cell density regulator HapR represses pathogen tryptophan consumption. This provides host enterocytes precursors for serotonin synthesis, which activates intestinal innate immune signaling and prolongs host survival. Thus, V. cholerae HapR promotes a commensal relationship with the host.