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Updated: Sep 13, 2025
Application of a Mouse Ligated Peyer’s Patch Intestinal Loop Assay to Evaluate Bacterial Uptake by M cells
Published on: December 17, 2011
Pyruvate-GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses
Katsuhiro Nakanishi1, Takayuki Ajiro1, Kaito Yukishima1
1Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Abstract:
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.
Insights
Bacterial pyruvate enhances intestinal immunity by activating lysozyme-expressing dendritic cells (LysoDCs) via G-protein coupled receptor 31 (GPR31). This boosts pathogen clearance and T cell responses, conferring resistance to infection.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Peyer's patches (PPs) are key for intestinal immunity, but antigen capture by underlying phagocytes is poorly understood.
- Microfold (M) cells in PPs transfer pathogens, but downstream immune cell activation mechanisms require elucidation.
Purpose of the Study:
- To investigate the role of bacterial metabolites in modulating antigen capture by mononuclear phagocytes in Peyer's patches.
- To elucidate the mechanism by which pyruvate influences dendritic cell function and intestinal immunity.
Main Methods:
- Administration of pyruvate to wild-type and GPR31-deficient mice orally infected with Listeria monocytogenes.
- Analysis of dendritic cell morphology, antigen uptake, gene expression, and migration patterns.
- Assessment of T cell responses (Th1, cytotoxic T cells) and host resistance to infection.
Main Results:
- Pyruvate induced specific dendritic cell (LysoDC) protrusions into M-cell pockets via GPR31.
- Pyruvate enhanced LysoDC uptake of Listeria monocytogenes in a GPR31-dependent manner.
- GPR31 signaling boosted antigen processing, altered gene expression, promoted LysoDC migration, and enhanced pathogen-specific T cell responses.
Conclusions:
- The pyruvate-GPR31 axis is crucial for orchestrating intestinal protective immunity.
- Pyruvate administration confers significant resistance to Listeria monocytogenes infection via GPR31-mediated immune activation.
- This study reveals a novel mechanism for bacterial metabolite-driven immune modulation in the gut.
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