Pyruvate–GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses

Pyruvate–GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses

Peyer’s patches (PPs) are sites of antigen entry and immunoinduction in the small intestine. In PPs, pathogens are transferred through microfold (M) cells; however, the mechanisms of antigen capture by mononuclear phagocytes beneath M cells remain unclear. Here, we demonstrate that bacterial metabol...

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Main Authors: Katsuhiro Nakanishi, Takayuki Ajiro, Kaito Yukishima, Yuki Tsukamoto, Junichi Kikuta, Shinichiro Sawa, Michio Tomura, Nozomi Kinoshita, Wataru Shimanuki, Akio Suzuki, Shun Arai, Kazuki Maeshima, Takumi Ichisawa, Tomoya Katakai, Haruko Hayasaka, Masaru Ishii, Eiji Umemoto
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Gut Microbes
Subjects:
Peyer’s patch
commensal metabolite
GPCR: dendritic cell
Listeria monocytogenes
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2025.2536089
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Summary:Peyer’s patches (PPs) are sites of antigen entry and immunoinduction in the small intestine. In PPs, pathogens are transferred through microfold (M) cells; however, the mechanisms of antigen capture by mononuclear phagocytes beneath M cells remain unclear. Here, we demonstrate that bacterial metabolite pyruvate acted on lysozyme-expressing dendritic cells (LysoDCs), a monocyte-derived phagocyte subset, and induced protrusion of dendrites particularly with “balloon” shapes into basolateral M-cell pockets via its receptor, G-protein coupled receptor 31 (GPR31). Pyruvate administration in wild-type but not Gpr31b-deficient mice increased LysoDC uptake of orally infected Listeria monocytogenes. GPR31 signaling boosted antigen processing and altered gene expression. It also increased LysoDC migration to the interfollicular region, thereby promoting production of pathogen-specific Th1 cells as well as cytotoxic T cells, and effector T cell migration to the lamina propria. Furthermore, oral pyruvate administration conferred high resistance to a virulent L. monocytogenes strain in a GPR31-dependent manner. Collectively, the pyruvate – GPR31 axis plays critical roles in orchestrating intestinal protective immunity.
ISSN:1949-0976
1949-0984

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