| RRC ID |
56335
|
| 著者 |
Morita N, Umemoto E, Fujita S, Hayashi A, Kikuta J, Kimura I, Haneda T, Imai T, Inoue A, Mimuro H, Maeda Y, Kayama H, Okumura R, Aoki J, Okada N, Kida T, Ishii M, Nabeshima R, Takeda K.
|
| タイトル |
GPR31-dependent dendrite protrusion of intestinal CX3CR1+ cells by bacterial metabolites.
|
| ジャーナル |
Nature
|
| Abstract |
Small intestinal mononuclear cells that express CX3CR1 (CX3CR1+ cells) regulate immune responses1-5. CX3CR1+ cells take up luminal antigens by protruding their dendrites into the lumen1-4,6. 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.
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| 巻・号 |
566(7742)
|
| ページ |
110-114
|
| 公開日 |
2019-2-1
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| DOI |
10.1038/s41586-019-0884-1
|
| PII |
10.1038/s41586-019-0884-1
|
| PMID |
30675063
|
| MeSH |
Animals
Bacteria / immunology
Bacteria / metabolism*
CX3C Chemokine Receptor 1 / deficiency
CX3C Chemokine Receptor 1 / genetics
CX3C Chemokine Receptor 1 / metabolism*
Cell Surface Extensions / drug effects
Cell Surface Extensions / immunology
Cell Surface Extensions / metabolism*
Female
HEK293 Cells
Humans
Intestine, Small / cytology*
Intestine, Small / drug effects
Intestine, Small / immunology
Intestine, Small / microbiology*
Lactic Acid / metabolism*
Lactic Acid / pharmacology
Lactobacillus helveticus / metabolism
Male
Methanol
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Pyruvic Acid / metabolism*
Pyruvic Acid / pharmacology
Receptors, G-Protein-Coupled / deficiency
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism*
Salmonella / immunology
Salmonella / metabolism
|
| IF |
43.07
|
| 引用数 |
26
|
| リソース情報 |
| 一般微生物 |
JCM 1112, JCM 1131, JCM 1152, JCM 1231, JCM 2012, JCM 5670, JCM 16172, JCM 1132, JCM 1012, JCM 1120, JCM 1185, JCM 17136, JCM 1192 |
