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

Priyanka Pundir, Rui Liu, Chirag Vasavda, Nadine Serhan, Nathachit Limjunyawong, Rebecca Yee, Yingzhuan Zhan, Xintong Dong, Xueqing Wu, Ying Zhang, Solomon H. Snyder, Nicolas Gaudenzio, Jorge E. Vidal, Xinzhong Dong

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)114-122.e8
JournalCell Host and Microbe
Volume26
Issue number1
DOIs
StatePublished - Jul 10 2019

Keywords

  • GPCR
  • Gram-positive bacteria
  • MRGPRX2
  • Mrgprb2
  • Mrgprs
  • bacterial infection
  • innate immunity
  • mast cell
  • quorum sensing
  • quorum sensing molecules

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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  • Cite this

    Pundir, P., Liu, R., Vasavda, C., Serhan, N., Limjunyawong, N., Yee, R., Zhan, Y., Dong, X., Wu, X., Zhang, Y., Snyder, S. H., Gaudenzio, N., Vidal, J. E., & Dong, X. (2019). A Connective Tissue Mast-Cell-Specific Receptor Detects Bacterial Quorum-Sensing Molecules and Mediates Antibacterial Immunity. Cell Host and Microbe, 26(1), 114-122.e8. https://doi.org/10.1016/j.chom.2019.06.003