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

Publication ,  Journal Article
Arifuzzaman, M; Mobley, YR; Choi, HW; Bist, P; Salinas, CA; Brown, ZD; Chen, SL; Staats, HF; Abraham, SN
Published in: Sci Adv
January 2019

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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Published In

Sci Adv

DOI

EISSN

2375-2548

Publication Date

January 2019

Volume

5

Issue

1

Start / End Page

eaav0216

Location

United States

Related Subject Headings

  • Wound Healing
  • Wasp Venoms
  • Transfection
  • Staphylococcus aureus
  • Staphylococcal Skin Infections
  • Receptors, Neuropeptide
  • Receptors, G-Protein-Coupled
  • Neutrophils
  • Nerve Tissue Proteins
  • Mice, Transgenic
 

Citation

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Arifuzzaman, M., Mobley, Y. R., Choi, H. W., Bist, P., Salinas, C. A., Brown, Z. D., … Abraham, S. N. (2019). MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection. Sci Adv, 5(1), eaav0216. https://doi.org/10.1126/sciadv.aav0216
Arifuzzaman, Mohammad, Yuvon R. Mobley, Hae Woong Choi, Pradeep Bist, Cristina A. Salinas, Zachary D. Brown, Swaine L. Chen, Herman F. Staats, and Soman N. Abraham. “MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection.Sci Adv 5, no. 1 (January 2019): eaav0216. https://doi.org/10.1126/sciadv.aav0216.
Arifuzzaman M, Mobley YR, Choi HW, Bist P, Salinas CA, Brown ZD, et al. MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection. Sci Adv. 2019 Jan;5(1):eaav0216.
Arifuzzaman, Mohammad, et al. “MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection.Sci Adv, vol. 5, no. 1, Jan. 2019, p. eaav0216. Pubmed, doi:10.1126/sciadv.aav0216.
Arifuzzaman M, Mobley YR, Choi HW, Bist P, Salinas CA, Brown ZD, Chen SL, Staats HF, Abraham SN. MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection. Sci Adv. 2019 Jan;5(1):eaav0216.

Published In

Sci Adv

DOI

EISSN

2375-2548

Publication Date

January 2019

Volume

5

Issue

1

Start / End Page

eaav0216

Location

United States

Related Subject Headings

  • Wound Healing
  • Wasp Venoms
  • Transfection
  • Staphylococcus aureus
  • Staphylococcal Skin Infections
  • Receptors, Neuropeptide
  • Receptors, G-Protein-Coupled
  • Neutrophils
  • Nerve Tissue Proteins
  • Mice, Transgenic