title: Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair.
abstract: Induction of macrophage necrosis is a strategy used by virulent Mycobacterium tuberculosis (Mtb) to avoid innate host defense. In contrast, attenuated Mtb causes apoptosis, which limits bacterial replication and promotes T cell cross-priming by antigen-presenting cells. Here we show that Mtb infection causes plasma membrane microdisruptions. Resealing of these lesions, a process crucial for preventing necrosis and promoting apoptosis, required translocation of lysosomal and Golgi apparatus-derived vesicles to the plasma membrane. Plasma membrane repair depended on prostaglandin E(2) (PGE(2)), which regulates synaptotagmin 7 (Syt-7), the calcium sensor involved in the lysosome-mediated repair mechanism. By inducing production of lipoxin A(4) (LXA(4)), which blocks PGE(2) biosynthesis, virulent Mtb prevented membrane repair and induced necrosis. Thus, virulent Mtb impairs macrophage plasma membrane repair to evade host defenses.
authors: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Maziar
authors: M
authors: Divangahi
authors: Minjian
authors: M
authors: Chen
authors: Huixian
authors: H
authors: Gan
authors: Danielle
authors: D
authors: Desjardins
authors: Tyler T
authors: TT
authors: Hickman
authors: David M
authors: DM
authors: Lee
authors: Sarah
authors: S
authors: Fortune
authors: Samuel M
authors: SM
authors: Behar
authors: Heinz G
authors: HG
authors: Remold
mesh_terms: D000818:Animals; D017209:Apoptosis; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D006056:Golgi Apparatus / Q000502:physiology; D006801:Humans; D044045:Lipoxins / Q000378:metabolism; D008247:Lysosomes / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D009336:Necrosis; D050857:Synaptotagmins / Q000378:metabolism; D014774:Virulence
chemical_list: D044045:Lipoxins; C494303:Syt7 protein, mouse; C040527:lipoxin A4; D050857:Synaptotagmins; D015232:Dinoprostone