Significance of Mast Cell Formed Extracellular Traps in Microbial Defense

Abstract

Mast cells (MCs) are critically involved in microbial defense by releasing antimicrobial peptides (such as cathelicidin LL-37 and defensins) and phagocytosis of microbes. In past years, it has become evident that in addition MCs may eliminate invading pathogens by ejection of web-like structures of DNA strands embedded with proteins known together as extracellular traps (ETs). Upon stimulation of resting MCs with various microorganisms, their products (including superantigens and toxins), or synthetic chemicals, MCs become activated and enter into a multistage process that includes disintegration of the nuclear membrane, release of chromatin into the cytoplasm, adhesion of cytoplasmic granules on the emerging DNA web, and ejection of the complex into the extracellular space. This so-called ETosis is often associated with cell death of the producing MC, and the type of stimulus potentially determines the ratio of surviving vs. killed MCs. Comparison of different microorganisms with specific elimination characteristics such as S pyogenes (eliminated by MCs only through extracellular mechanisms), S aureus (removed by phagocytosis), fungi, and parasites has revealed important aspects of MC extracellular trap (MCET) biology. Molecular studies identified that the formation of MCET depends on NADPH oxidase-generated reactive oxygen species (ROS). In this review, we summarize the present state-of-the-art on the biological relevance of MCETosis, and its underlying molecular and cellular mechanisms. We also provide an overview over the techniques used to study the structure and function of MCETs, including electron microscopy and fluorescence microscopy using specific monoclonal antibodies (mAbs) to detect MCET-associated proteins such as tryptase and histones, and cell-impermeant DNA dyes for labeling of extracellular DNA. Comparing the type and biofunction of further MCET decorating proteins with ETs produced by other immune cells may help provide a better insight into MCET biology in the pathogenesis of autoimmune and inflammatory disorders as well as microbial defense.

Uncovering the Mast Cell Response to Mycobacterium tuberculosis

“…These are antimicrobial structures that support extracellular killing of bacteria that have not been efficiently phagocytized. MECTs act through a combination of direct killing of entrapped pathogens and/or physical retention so that phagocytic cells recruited to the infection site can then eliminate the pathogen ( 38 ). These structures were first described in other cell types, including neutrophils ( 39 ).…”

Protease Profile of Tumor-Associated Mast Cells in Melanoma

“…In accordance with the content of proteases, MCs in the skin are representatives of the subpopulation expressing CPA3, tryptase, and chymase [ 37 , 38 , 39 ]. Many biomarkers have been developed in clinical practice to improve the diagnosis and prognosis of some neoplasms.…”

The emerging role of mast cells in skin cancers: involved cellular and molecular mechanisms

“…Mast cells are the granular cells of the innate immune system that originate from CD34 + /CD117 + bone marrow progenitor cells 19 . These progenitors are derived from bone marrow and find their way through the circulation into target tissues 20,21 . Under the influence of the growth factors, mainly SCF, the progenitors complete their final maturation stages 22 .…”

“…19 These progenitors are derived from bone marrow and find their way through the circulation into target tissues. 20,21 Under the influence of the growth factors, mainly SCF, the progenitors complete their final maturation stages. 22 According to the protease content, human MCs are classically classified into two subpopulations, namely MC T subclass that expresses tryptase only and MC TC subclass that expresses carboxypeptidase A3 (CPA3), tryptase, and chymase.…”