A Connective Tissue Mast-Cell-Specific Receptor Detects Bacterial Quorum-Sensing Molecules and Mediates Antibacterial Immunity

• Type of Material: Article
• Authors: Priyanka Pundir, Johns Hopkins University; Rui Liu, Johns Hopkins University; Chirag Vasavda, Johns Hopkins University; Nadine Serhan, Universite de Toulouse; Nathachut Limjunyawong, Johns Hopkins University; Rebecca Yee, Johns Hopkins University; Yingzhuan Zhan, Johns Hopkins University; Xintong Dong, Johns Hopkins University; Xueqing Wu, Emory University; Ying Zhang, Johns Hopkins University; Solomon H. Snyder, Johns Hopkins University; Nicolas Gaudenzio, Universite de Toulouse; Jorge Vidal Graniel, Emory University; Xinzhong Dong, Johns Hopkins University
• Language: English
• Date: 2019-07-10
• Publisher: Cell Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chom.2019.06.003
• Title of Journal or Parent Work: Cell Host and Microbe
• Volume: 26
• Issue: 1
• Start Page: 114
• End Page: +
• Grant/Funding Information: The work was supported by grants from the NIH to X.D. (NS054791 and AI135186), J.E.V. (R21AI112768-01A1), S.H.S (MH18501), and C.V. (T32GM73009).; P.P. received a Canadian Institutes of Health Research Fellowship.; N.G. is supported by the Société Française de Dermatologie, the Société Française d’Allergologie, the Marie Skłodowska-Curie Individual Fellowship (H2020-MSCA-IF-2016 #749629), the European Research Council (ERC-2018-STG #802041), and the INSERM.
• Keywords: Parasitology; Competence; Science & Technology; Signals; Virology; Binding; Responses; Pertussin-toxin; Life Sciences & Biomedicine; Protein; Antimicrobial peptides; Activation; Microbiology
• Research Categories: Biology, Parasitology; Biology, Virology; Biology, Microbiology

Abstract

Quorum-sensing molecules (QSMs) are secreted by bacteria to signal population density. Upon reaching a critical concentration, QSMs induce transcriptional alterations in bacteria, which 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 homolog MRGPRX2 are receptors for Gram-positive QSMs, including competence-stimulating peptide (CSP)-1. CSP-1 activates Mrgprb2 and MRGPRX2, triggering mast cell degranulation, which inhibits bacterial growth and prevents biofilm formation. Such antibacterial functions are reduced in Mrgprb2-deficient mast cells, while wild-type 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. Bacteria use quorum-sensing signaling for cross-species communication. Pundir et al. report that host mast cells detect Gram-positive-bacteria-derived quorum-sensing molecules via the Mrgpr receptors. Mrgpr activation triggers antibacterial activity and immune cell recruitment to efficiently clear bacteria, while animals deficient in Mrgpr are hypersusceptible to bacterial infection.