title: Mycobacterium massiliense Induces Macrophage Extracellular Traps with Facilitating Bacterial Growth.
abstract: Human neutrophils have been known to release neutrophil extracellular traps (NETs), antimicrobial DNA structures capable of capturing and killing microbes. Recently, a similar phenomenon has been reported in macrophages infected with various pathogens. However, a role for macrophages extracellular traps (METs) in host defense responses against Mycobacterium massiliense (M. mass) has yet to be described. In this study, we show that M. mass, a rapid growing mycobacterium (RGM), also induces the release of METs from PMA-differentiated THP-1 cells. Intriguingly, this process is not dependent on NADPH oxidase activity, which regulates NET formation. Instead, M. mass-induced MET formation partially depends on calcium influx and requires phagocytosis of high bacterial load. The METs consist of a DNA backbone embedded with microbicidal proteins such as histone, MPO and elastase. Released METs entrap M. mass and prevent their dissemination, but do not have bactericidal activity. Instead, they result in enhanced bacterial growth. In this regard, METs were considered to provide interaction of M. mass with cells and an environment for bacterial aggregation, which may facilitate mycobacterial survival and growth. In conclusion, our results demonstrate METs as an innate defense response against M. mass infection, and suggest that extracellular traps play a multifaceted role in the interplay between host and bacteria.
authors.affiliation: Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Sungmo
authors.initials: S
authors.lastname: Je
authors.affiliation: Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Hailian
authors.initials: H
authors.lastname: Quan
authors.affiliation: Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Yina
authors.initials: Y
authors.lastname: Yoon
authors.affiliation: Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Yirang
authors.initials: Y
authors.lastname: Na
authors.affiliation: Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Seung Hyeok
authors.initials: SH
authors.lastname: Seok
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D015415:Biomarkers; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004272:DNA, Mitochondrial / Q000378:metabolism; D065206:Extracellular Traps / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D050296:Microbial Viability / Q000276:immunology; D009161:Mycobacterium / Q000502:physiology*; D019255:NADPH Oxidases / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015415:Biomarkers; D016207:Cytokines; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D010196:Pancreatic Elastase; D002118:Calcium