Editors' ChoiceHost-Microbe Interactions

Mast cells tune in to quorum sensing

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Science Signaling  13 Aug 2019:
Vol. 12, Issue 594, eaaz0499
DOI: 10.1126/scisignal.aaz0499

The molecules that bacteria use to coordinate virulence-promoting collective behaviors also activate mast cells.

When activated by stimuli such as allergens or damage- or pathogen-associated molecular patterns (see also Kawakami and Kasakura), mast cells degranulate, releasing stores of histamine, cytokines, and proteases that protect the organism from infection and initiate allergic reactions. Pundir et al. have found that mast cells also respond to bacterial quorum-sensing molecules (QSMs), which are secreted factors that drive the expression of genes involved in virulence and biofilm formation. From a panel of bacteria-derived molecules, the authors identified several cationic peptide QSMs from Gram-positive bacteria as activators of the mouse mast cell receptor MAS-related G protein–coupled receptor B2 (Mrgprb2) and its human ortholog, MRGPRX2. Mrgprb2 and MRGPRX2 were required in primary mouse peritoneal mast cells and cultured human LAD2 mast cells, respectively, for maximal killing of both planktonic and biofilm-associated Streptococcus pneumoniae that produced the QSM competence-stimulating peptide 1 (CSP-1). Neither mouse nor human mast cells effectively killed mutant S. pneumoniae that did not make CSP-1. MRGPRX2 and Mrgprb2 were required for mast cell responses to wild-type S. pneumoniae in LAD2 cells in vitro and in resident nasopharynx mast cells in vivo. Compared with wild-type controls, mice lacking Mrgprb2 were more susceptible to S. pneumoniae infection of the nasopharynx, Enterococcus faecium infection of the peritoneum, and Streptococcus pyogenes infection of the skin. Stimulating mast cells by injecting infected mice with CSP-1 or the Mrgprb2 agonist 48/80 resulted in reduced numbers of bacteria in both peritoneal and skin infection models. Given that Mrgprb2 and MRGPRX2 can also be activated by various cationic chemical compounds, it may be possible to exploit this system for treating bacterial infections.

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