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In vitro resistance mechanisms of N eisseria meningitidis against neutrophil extracellular traps
Author(s) -
Lappann Martin,
Danhof Sophia,
Guenther Frank,
OlivaresFlorez Silvana,
Mordhorst Ines Louise,
Vogel Ulrich
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12288
Subject(s) - neutrophil extracellular traps , neisseria meningitidis , biology , microbiology and biotechnology , phagocytosis , innate immune system , in vivo , bacterial outer membrane , immunity , microvesicles , extracellular , bacteria , immunology , immune system , inflammation , biochemistry , gene , escherichia coli , microrna , genetics
Summary N eisseria meningitidis ( N m) is a leading cause of septicemia in childhood. N m septicemia is unique with respect to very quick disease progression, high in vivo bacterial replication rate and its considerable mortality. N m 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 N m 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 N m 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 N m from NET ‐bound cathepsin G ; (ii) expression of the high‐affinity zinc uptake receptor ZnuD allowed N m to escape NET ‐mediated nutritional immunity; (iii) binding of SOMVs to NETs saved N m 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 N m in vivo might aggravate thrombosis in vessels ultimately directing to disseminated intravascular coagulation ( DIC ).