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Sci Adv. 2019 Jan 2;5(1):eaav0216. doi: 10.1126/sciadv.aav0216. eCollection 2019 Jan.

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

Author information

1
Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
2
Department of Pathology, Duke University, Durham, NC 27710, USA.
3
Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, Singapore.
4
Undergraduate Program in Biology, Duke University, Durham, NC 27710, USA.
5
Undergraduate Program in Biomedical Engineering, Duke University, Durham, NC 27710, USA.
6
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
7
Infectious Diseases Group, Genome Institute of Singapore, Singapore 138672, Singapore.
8
Department of Immunology, Duke University, Durham, NC 27710, USA.
9
Department of Medicine, Duke University, Durham, NC 27710, USA.

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.

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