1. A Connective Tissue Mast-Cell-Specific Receptor Detects Bacterial Quorum-Sensing Molecules and Mediates Antibacterial Immunity
- Author
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Xinzhong Dong, Nadine Serhan, Ying Zhang, Rebecca Yee, Xueqing Wu, Xintong Dong, Priyanka Pundir, Nathachit Limjunyawong, Solomon H. Snyder, Yingzhuan Zhan, Jorge E. Vidal, Chirag Vasavda, Rui Liu, Nicolas Gaudenzio, Johns Hopkins University School of Medicine [Baltimore], Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Emory University [Atlanta, GA], and Pistre, Karine
- Subjects
Receptors, Neuropeptide ,MESH: Immunity, Innate ,Enterococcus faecium ,MESH: Nerve Tissue Proteins / metabolism ,Mrgprs ,MESH: Mast Cells / immunology ,MESH: Mice, Knockout ,Virulence factor ,Receptors, G-Protein-Coupled ,Mice ,GPCR ,0302 clinical medicine ,Bacteriocins ,MESH: Streptococcus pneumoniae / immunology ,MESH: Animals ,Mast Cells ,Receptor ,innate immunity ,MESH: Bacteriocins / metabolism ,Mice, Knockout ,0303 health sciences ,MESH: Bacterial Proteins / metabolism ,Degranulation ,quorum sensing ,Gram-positive bacteria ,MESH: Receptors, Neuropeptide / metabolism ,Mast cell ,Anti-Bacterial Agents ,Cell biology ,Streptococcus pneumoniae ,medicine.anatomical_structure ,Connective Tissue ,MESH: Enterococcus faecium / immunology ,MRGPRX2 ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,MESH: Streptococcus pyogenes / immunology ,Streptococcus pyogenes ,Nerve Tissue Proteins ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Microbiology ,Article ,Mrgprb2 ,03 medical and health sciences ,Bacterial Proteins ,Virology ,medicine ,Animals ,Humans ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,MESH: Mice ,030304 developmental biology ,G protein-coupled receptor ,MESH: Humans ,Innate immune system ,Bacteria ,bacterial infection ,MESH: Receptors, G-Protein-Coupled / metabolism ,Biofilm ,quorum sensing molecules ,MESH: Connective Tissue / immunology ,Immunity, Innate ,Quorum sensing ,Parasitology ,mast cell ,030217 neurology & neurosurgery - Abstract
International audience; Quorum sensing molecules (QSMs) are secreted by bacteria to signal population density. Upon reaching a critical concentration, QSMs induce transcriptional alterations in bacteria that enable virulence factor expression and biofilm formation. It is unclear whether mammalian hosts can recognize QSMs to trigger responsive antibacterial immunity. We report that mouse mast cell-specific G protein-coupled-receptor Mrgprb2, and its human homologue MRGPRX2, are receptors for Gram-positive QSMs, including competence-stimulating peptide (CSP)-1. CSP-1 activates Mrgprb2/MRGPRX2, triggering mast cell degranulation which inhibits bacterial growth and prevents biofilm formation. Such antibacterial functions are reduced in Mrgprb2-deficient mast cells, while wildtype mast cells fail to inhibit the growth of bacterial strains lacking CSP-1. Mrgprb2-knockout mice exhibit reduced bacterial clearance, while pharmacologically activating Mrgprb2 in vivo eliminates bacteria and improves disease score. These findings identify a host defense mechanism that uses QSMs as an “Achilles heel” and suggest MRGPRX2 as a potential therapeutic target for controlling bacterial infections.
- Published
- 2019
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