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

Arifuzzaman, Mohammad

Mobley, Yuvon R

Choi, Hae Woong

Bist, Pradeep

Salinas, Cristina A

Brown, Zachary D

Chen, Swaine L

Staats, Herman F

Abraham, Soman N

2019-02-01T14:51:32Z

2019-02-01T14:51:32Z

2019-01-02

2019-02-01T14:51:28Z

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.

aav0216

2375-2548

2375-2548

https://hdl.handle.net/10161/17955

eng

American Association for the Advancement of Science (AAAS)

Science advances

10.1126/sciadv.aav0216

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

Journal article

Staats, Herman F|0000-0003-1039-1087

eaav0216

1

School of Medicine

Duke

Duke Human Vaccine Institute

Institutes and Centers

Immunology

Basic Science Departments

Pathology

Clinical Science Departments

Duke Cancer Institute

Molecular Genetics and Microbiology

Published

5