title: Phagocytosis-independent antimicrobial activity of mast cells by means of extracellular trap formation.
abstract: These days it has been increasingly recognized that mast cells (MCs) are critical components of host defense against pathogens. In this study, we have provided the first evidence that MCs can kill bacteria by entrapping them in extracellular structures similar to the extracellular traps described for neutrophils (NETs). We took advantage of the ability of MCs to kill the human pathogen Streptococcus pyogenes by a phagocytosis-independent mechanism in order to characterize the extracellular antimicrobial activity of MCs. Close contact of bacteria and MCs was required for full antimicrobial activity. Immunofluorescence and electron microscopy revealed that S pyogenes was entrapped by extracellular structures produced by MCs (MCETs), which are composed of DNA, histones, tryptase, and the antimicrobial peptide LL-37. Disruption of MCETs significantly reduced the antimicrobial effect of MCs, suggesting that intact extracellular webs are critical for effective inhibition of bacterial growth. Similar to NETs, production of MCETs was mediated by a reactive oxygen species (ROS)-dependent cell death mechanism accompanied by disruption of the nuclear envelope, which can be induced after stimulation of MCs with phorbol-12-myristate-13-acetate (PMA), H(2)O(2), or bacterial pathogens. Our study provides the first experimental evidence of antimicrobial extracellular traps formation by an immune cell population other than neutrophils.
authors.affiliation: Infection Immunology Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: von Köckritz-Blickwede
authors.forename: Oliver
authors.initials: O
authors.lastname: Goldmann
authors.forename: Pontus
authors.initials: P
authors.lastname: Thulin
authors.forename: Katja
authors.initials: K
authors.lastname: Heinemann
authors.forename: Anna
authors.initials: A
authors.lastname: Norrby-Teglund
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Eva
authors.initials: E
authors.lastname: Medina
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis; D016923:Cell Death; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005110:Extracellular Space / Q000276:immunology*; D005260:Female; D006801:Humans; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure*; D051379:Mice; D050296:Microbial Viability; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D019255:NADPH Oxidases / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D013297:Streptococcus pyogenes / Q000166:cytology / Q000276:immunology / Q000472:pathogenicity; D053802:Tryptases / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D004247:DNA; D019255:NADPH Oxidases; D053802:Tryptases; D054804:Cathelicidins