In vitro resistance mechanisms of N eisseria meningitidis against neutrophil extracellular traps

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 ).