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GPR31-dependent dendrite protrusion of intestinal CX3CR1 + cells by bacterial metabolites
Nature (London), 2019-02, Vol.566 (7742), p.110-3
2019

Details

Autor(en) / Beteiligte
Titel
GPR31-dependent dendrite protrusion of intestinal CX3CR1 + cells by bacterial metabolites
Ist Teil von
  • Nature (London), 2019-02, Vol.566 (7742), p.110-3
Ort / Verlag
England: Nature Publishing Group
Erscheinungsjahr
2019
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • Small intestinal mononuclear cells that express CX3CR1 (CX3CR1 cells) regulate immune responses . CX3CR1 cells take up luminal antigens by protruding their dendrites into the lumen . However, it remains unclear how dendrite protrusion by CX3CR1 cells is induced in the intestine. Here we show in mice that the bacterial metabolites pyruvic acid and lactic acid induce dendrite protrusion via GPR31 in CX3CR1 cells. Mice that lack GPR31, which was highly and selectively expressed in intestinal CX3CR1 cells, showed defective dendrite protrusions of CX3CR1 cells in the small intestine. A methanol-soluble fraction of the small intestinal contents of specific-pathogen-free mice, but not germ-free mice, induced dendrite extension of intestinal CX3CR1 cells in vitro. We purified a GPR31-activating fraction, and identified lactic acid. Both lactic acid and pyruvic acid induced dendrite extension of CX3CR1 cells of wild-type mice, but not of Gpr31b mice. Oral administration of lactate and pyruvate enhanced dendrite protrusion of CX3CR1 cells in the small intestine of wild-type mice, but not in that of Gpr31b mice. Furthermore, wild-type mice treated with lactate or pyruvate showed an enhanced immune response and high resistance to intestinal Salmonella infection. These findings demonstrate that lactate and pyruvate, which are produced in the intestinal lumen in a bacteria-dependent manner, contribute to enhanced immune responses by inducing GPR31-mediated dendrite protrusion of intestinal CX3CR1 cells.
Sprache
Englisch
Identifikatoren
ISSN: 0028-0836
eISSN: 1476-4687
DOI: 10.1038/s41586-019-0884-1
Titel-ID: cdi_proquest_journals_2184025878
Format
–
Schlagworte
Acids, Animals, Antigens, Bacteria, Bacteria - immunology, Bacteria - metabolism, Cell Surface Extensions - drug effects, Cell Surface Extensions - immunology, Cell Surface Extensions - metabolism, CX3C Chemokine Receptor 1 - deficiency, CX3C Chemokine Receptor 1 - genetics, CX3C Chemokine Receptor 1 - metabolism, CX3CR1 protein, Dendrites, Dendritic cells, Dendritic structure, Fatty acids, Female, Genes, Germfree, HEK293 Cells, High resistance, Humans, Immune response, Immune system, Infections, Intestine, Small - cytology, Intestine, Small - drug effects, Intestine, Small - immunology, Intestine, Small - microbiology, Lactic acid, Lactic Acid - metabolism, Lactic Acid - pharmacology, Lactobacillus helveticus - metabolism, Leukocytes (mononuclear), Ligands, Male, Metabolites, Methanol, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, Microbiota, Oral administration, Proteins, Pyruvic acid, Pyruvic Acid - metabolism, Pyruvic Acid - pharmacology, Receptors, G-Protein-Coupled - deficiency, Receptors, G-Protein-Coupled - genetics, Receptors, G-Protein-Coupled - metabolism, Rodents, Salmonella, Salmonella - immunology, Salmonella - metabolism, Small intestine, Stem cells

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