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

ABSTRACT: 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.

SUBMITTER: Jugder BE

PROVIDER: S-EPMC9534793 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Jugder Bat-Erdene BE Batista Juliana H JH Gibson Jacob A JA Cunningham Paul M PM Asara John M JM Watnick Paula I PI

Cell reports 20220901 12

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. ...[more]

PMID: 36130487

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Project description:UnlabelledFarnesol, produced by the polymorphic fungus Candida albicans, is the first quorum-sensing molecule discovered in eukaryotes. Its main function is control of C. albicans filamentation, a process closely linked to pathogenesis. In this study, we analyzed the effects of farnesol on innate immune cells known to be important for fungal clearance and protective immunity. Farnesol enhanced the expression of activation markers on monocytes (CD86 and HLA-DR) and neutrophils (CD66b and CD11b) and promoted oxidative burst and the release of proinflammatory cytokines (tumor necrosis factor alpha [TNF-?] and macrophage inflammatory protein 1 alpha [MIP-1?]). However, this activation did not result in enhanced fungal uptake or killing. Furthermore, the differentiation of monocytes to immature dendritic cells (iDC) was significantly affected by farnesol. Several markers important for maturation and antigen presentation like CD1a, CD83, CD86, and CD80 were significantly reduced in the presence of farnesol. Furthermore, farnesol modulated migrational behavior and cytokine release and impaired the ability of DC to induce T cell proliferation. Of major importance was the absence of interleukin 12 (IL-12) induction in iDC generated in the presence of farnesol. Transcriptome analyses revealed a farnesol-induced shift in effector molecule expression and a down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor during monocytes to iDC differentiation. Taken together, our data unveil the ability of farnesol to act as a virulence factor of C. albicans by influencing innate immune cells to promote inflammation and mitigating the Th1 response, which is essential for fungal clearance.ImportanceFarnesol is a quorum-sensing molecule which controls morphological plasticity of the pathogenic yeast Candida albicans. As such, it is a major mediator of intraspecies communication. Here, we investigated the impact of farnesol on human innate immune cells known to be important for fungal clearance and protective immunity. We show that farnesol is able to enhance inflammation by inducing activation of neutrophils and monocytes. At the same time, farnesol impairs differentiation of monocytes into immature dendritic cells (iDC) by modulating surface phenotype, cytokine release and migrational behavior. Consequently, iDC generated in the presence of farnesol are unable to induce proper T cell responses and fail to secrete Th1 promoting interleukin 12 (IL-12). As farnesol induced down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, desensitization to GM-CSF could potentially explain transcriptional reprofiling of iDC effector molecules. Taken together, our data show that farnesol can also mediate Candida-host communication and is able to act as a virulence factor.

Dataset Information

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

Publications

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

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