title: In vitro resistance mechanisms of Neisseria meningitidis against neutrophil extracellular traps.
abstract: Neisseria meningitidis (Nm) is a leading cause of septicemia in childhood. Nm septicemia is unique with respect to very quick disease progression, high in vivo bacterial replication rate and its considerable mortality. Nm circumvents major mechanisms of innate immunity such as complement system and phagocytosis. Neutrophil extracellular traps (NETs) are formed from neutrophils during systemic infection and are suggested to contain invading microorganisms. Here, we investigated the interaction of Nm with NETs. Both, meningococci and spontaneously released outer membrane vesicles (SOMVs) were potent NET inducers. NETs were unable to kill NET bound meningococci, but slowed down their proliferation rate. Using Nm as model organism we identified three novel mechanisms how bacteria can evade NET-mediated killing: (i) modification of lipid A of meningococcal LPS with phosphoethanolamine protected Nm from NET-bound cathepsin G; (ii) expression of the high-affinity zinc uptake receptor ZnuD allowed Nm to escape NET-mediated nutritional immunity; (iii) binding of SOMVs to NETs saved Nm from NET binding and the consequent bacteriostatic effect. Escape from NETs may contribute to the most rapid progression of meningococcal disease. The induction of NET formation by Nm in vivo might aggravate thrombosis in vessels ultimately directing to disseminated intravascular coagulation (DIC).
authors.affiliation: Institute for Hygiene and Microbiology, University of Wuerzburg, Wuerzburg, Germany. mlappann@hygiene.uni-wuerzburg.de
authors.forename: Martin
authors.initials: M
authors.lastname: Lappann
authors.forename: Sophia
authors.initials: S
authors.lastname: Danhof
authors.forename: Frank
authors.initials: F
authors.lastname: Guenther
authors.forename: Silvana
authors.initials: S
authors.lastname: Olivares-Florez
authors.forename: Ines Louise
authors.initials: IL
authors.lastname: Mordhorst
authors.forename: Ulrich
authors.initials: U
authors.lastname: Vogel
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism; D056649:Cathepsin G / Q000276:immunology; D027682:Cation Transport Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004983:Ethanolamines / Q000737:chemistry; D010861:Fimbriae, Bacterial / Q000502:physiology; D055786:Gene Knockout Techniques; D006098:Granulocytes / Q000276:immunology / Q000382:microbiology; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D008050:Lipid A / Q000737:chemistry; D008589:Meningococcal Infections / Q000276:immunology; D046529:Microscopy, Electron, Transmission; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D015032:Zinc / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D004983:Ethanolamines; D008050:Lipid A; C553584:ZnuD protein, Neisseria meningitidis; C005448:phosphorylethanolamine; D056649:Cathepsin G; D015032:Zinc