MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection.
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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.
Published Version (Please cite this version)10.1126/sciadv.aav0216
Publication InfoStaats, Herman; Abraham, Soman; Arifuzzaman, Mohammad; Mobley, Yuvon R; Choi, Hae Woong; Bist, Pradeep; ... Chen, Swaine L (2019). MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection. Science advances, 5(1). pp. eaav0216. 10.1126/sciadv.aav0216. Retrieved from https://hdl.handle.net/10161/17955.
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Grace Kerby Professor of Pathology
The Abraham laboratory is interested in developing innovative approaches for curbing microbial infections through the study of the molecular interactions occurring between pathogenic bacteria and prominent immune and epithelial cells. We believe that there is a significant amount of crosstalk occurring between bacteria and host cells during infection and that the outcome of this interaction dictates both how quickly the infection is cleared and the severity of the pathology associated with th
Professor of Pathology
Areas of Research Interest: Our laboratory studies methods to induce and regulate antigen-specific immune responses at the mucosal surfaces of the host. The mucosal tissues and surfaces are often the first site of contact with infectious agents, a common location of life-threatening cancers and in constant contact with environmental antigens. A better understanding of factors that control the induction and regulation of mucosal immune responses may aid the development
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