MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection

Mohammad Arifuzzaman, Yuvon R. Mobley, Hae Woong Choi, Pradeep Bist, Cristina A. Salinas, Zachary D. Brown, Swaine L. Chen, Herman F. Staats, Soman N. Abraham

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Mast cells (MCs) are strategically distributed at barrier sites and prestore various immunocyte-recruiting cytokines, making them ideal targets for selective activation to treat peripheral infections. Here, we report that topical treatment with mastoparan, a peptide MC activator (MCA), enhances clearance of Staphylococcus aureus from infected mouse skins and accelerates healing of dermonecrotic lesions. Mastoparan functions by activating connective tissue MCs (CTMCs) via the MRGPRX2 (Mas-related G protein-coupled receptor member X2) receptor. Peripheral CTMC activation, in turn, enhances recruitment of bacteria-clearing neutrophils and wound-healing CD301b + dendritic cells. Consistent with MCs playing a master coordinating role, MC activation also augmented migration of various antigen-presenting dendritic cells to draining lymph nodes, leading to stronger protection against a second infection challenge. MCAs therefore orchestrate both the innate and adaptive immune arms, which could potentially be applied to combat peripheral infections by a broad range of pathogens.

Original languageEnglish
Article numbereaav0216
JournalScience Advances
Volume5
Issue number1
DOIs
Publication statusPublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • General

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