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Front. Immunol. | doi: 10.3389/fimmu.2018.00327

Group A Streptococcus Prevents Mast Cell Degranulation to Promote Extracellular Trap Formation

  • 1Biology Department, Occidental College, United States

The resurgence of Group A Streptococcus (GAS) infections in the past two decades has been a rising major public health concern. Due to a large number of GAS infections occurring in the skin, mast cells (MCs), innate immune cells known to localize to the dermis, could play an important role in controlling infection. MCs can exert their antimicrobial activities either early during infection, by degranulation and release of antimicrobial proteases and the cathelicidin-derived antimicrobial peptide LL-37, or by forming antibacterial MC extracellular traps (MCETs) in later stages of infection. We demonstrate that MCs do not directly degranulate in response to GAS, reducing their ability to control bacterial growth in early stages of infection. However, MC granule components are highly cytotoxic to GAS due to the pore-forming activity of LL-37, while MC granule proteases do not significantly affect GAS viability. We therefore confirmed the importance of MCETs by demonstrating their capacity to reduce GAS survival. The data therefore suggests that LL-37 from MC granules become embedded in MCETs, and are the primary effector molecule by which MCs control GAS infection. Our work underscores the importance of a non-traditional immune effector cell, utilizing a non-conventional mechanism, in the defense against an important human pathogen.

Keywords: group A streptococcus, Mast Cells, Cathelicidin, granules, extracellular traps, Cathepsin G

Received: 25 Oct 2017; Accepted: 06 Feb 2018.

Edited by:

Marina De Bernard, Università degli Studi di Padova, Italy

Reviewed by:

Barbara Frossi, University of Udine, Italy
Sushil K. Mahata, University of California, San Diego, United States  

Copyright: © 2018 Clark, Kim, Etesami, Shimamoto, Whalen, Martin and Okumura. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Cheryl Y. Okumura, Occidental College, Biology Department, 1600 Campus Rd., Los Angeles, 90041, California, United States, okumura@oxy.edu