title: Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation.
abstract: Mycobacterium abscessus is a rapidly growing Mycobacterium causing a wide spectrum of clinical syndromes. It now is recognized as a pulmonary pathogen to which cystic fibrosis patients have a particular susceptibility. The M. abscessus rough (R) variant, devoid of cell-surface glycopeptidolipids (GPLs), causes more severe clinical disease than the smooth (S) variant, but the underlying mechanisms of R-variant virulence remain obscure. Exploiting the optical transparency of zebrafish embryos, we observed that the increased virulence of the M. abscessus R variant compared with the S variant correlated with the loss of GPL production. The virulence of the R variant involved the massive production of serpentine cords, absent during S-variant infection, and the cords initiated abscess formation leading to rapid larval death. Cording occurred within the vasculature and was highly pronounced in the central nervous system (CNS). It appears that M. abscessus is transported to the CNS within macrophages. The release of M. abscessus from apoptotic macrophages initiated the formation of cords that grew too large to be phagocytized by macrophages or neutrophils. This study is a description of the crucial role of cording in the in vivo physiopathology of M. abscessus infection and emphasizes cording as a mechanism of immune evasion.
authors.affiliation: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5235, Université Montpellier 2, 34095 Montpellier, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Bernut
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Herrmann
authors.forename: Karima
authors.initials: K
authors.lastname: Kissa
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dubremetz
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Gaillard
authors.forename: Georges
authors.initials: G
authors.lastname: Lutfalla
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
mesh_terms: D000038:Abscess / Q000503:physiopathology*; D000818:Animals; D004002:Clodronic Acid; D003311:Cord Factors / Q000276:immunology / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004625:Embryo, Nonmammalian; D006017:Glycolipids / Q000378:metabolism*; D006020:Glycopeptides / Q000378:metabolism*; D006651:Histocytochemistry; D007091:Image Processing, Computer-Assisted; D007155:Immunologic Factors / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008856:Microscopy, Fluorescence; D060172:Morpholinos / Q000008:administration & dosage / Q000235:genetics; D009161:Mycobacterium / Q000166:cytology / Q000378:metabolism / Q000472:pathogenicity*; D009164:Mycobacterium Infections / Q000503:physiopathology*; D010587:Phagocytosis / Q000502:physiology; D014774:Virulence; D015027:Zebrafish
chemical_list: D003311:Cord Factors; D017931:DNA Primers; D006017:Glycolipids; D006020:Glycopeptides; D007155:Immunologic Factors; D060172:Morpholinos; C010762:peptidoglycolipids; D004002:Clodronic Acid
keywords: granuloma; innate immunity; morphotype; pathogenesis