Antimicrobial Activity of Mast Cells: Role and Relevance of Extracellular DNA Traps

Abstract

Mast cells (MCs) have been shown to release their nuclear DNA and subsequently form mast cell extracellular traps (MCETs) comparable to neutrophil extracellular traps, which are able to entrap and kill various microbes. The formation of extracellular traps is associated with the disruption of the nuclear membrane, which leads to mixing of nuclear compounds with granule components and causes the death of the cell, a process called ETosis. The question arises why do MCs release MCETs although they are very well known as multifunctional long-living sentinel cells? MCs are known to play a role during allergic reactions and certain parasitic infections. Nonetheless, they are also critical components of the early host innate immune response to bacterial and fungal pathogens: MCs contribute to the initiation of the early immune response by recruiting effector cells including neutrophils and macrophages by locally releasing inflammatory mediators, such as TNF-α. Moreover, various studies demonstrate that MCs are able to eliminate microbes through intracellular as well as extracellular antimicrobial mechanisms, including MCET formation similar to that of professional phagocytes. Recent literature leads to the suggestion that MCET formation is not the result of a passive release of DNA and granule proteins during cellular disintegration, but rather an active and controlled process in response to specific stimulation, which contributes to the innate host defense. This review will discuss the different known aspects of the antimicrobial activities of MCs with a special focus on MCETs, and their role and relevance during infection and inflammation.

Evidence for multiple modes of neutrophil serine protease recognition by the EAP family of Staphylococcal innate immune evasion proteins

“…While this result was unexpected, our observation that S. aureus secretes several high‐affinity inhibitors of MCC suggests a potentially important contribution of mast cells in the innate immune response against S. aureus infection. Indeed, roles in both phagocytic and non‐phagocytic killing of bacteria by mast cells have been described . In the future, additional work may provide the proper biological context for understanding MCC inhibition by staphylococcal EAP domain proteins and its impact on bacterial virulence and survival within the host.…”

Regulation of the pleiotropic effects of tissue-resident mast cells

“…A further twist of the defense strategies used by MCs, although suicidal, is formation of extracellular traps. 183 Here MCs release DNA to trap microbes that stick to the viscous material. The MCs die, but this process is not accidental but rather a programmed mechanism that apparently involves high reactive oxygen species production.…”

Macrophage Extracellular Traps: A Scoping Review

“…ETosis comprises a unique series of cellular events by which nuclear contents, including chromatin, mix with cellular proteins and are then extruded from the cell body to form extracellular structures capable of "trapping" and killing microorganisms [5][6][7]. Since the original report about neutrophils, other leukocytes including mast cells, eosinophils, and basophils are now known to produce "extracellular trap" structures [8][9][10][11][12]. ETs have been implicated in diverse disease states ranging from conditions of aseptic inflammation, such as gout, to vascular disorders including preeclampsia and thrombosis [13][14][15][16].…”