A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa

Abstract

Key Points Saliva induces bactericidal and DNase resistant NETs in the oral cavity via sialyl LewisX- L-selectin signaling. Disordered homeostasis in the oral cavity may lead to deficient saliva-mediated NETosis.

Neutrophil extracellular traps — the dark side of neutrophils

“…Dissolution of NETs by DNase, long after the NET-exposed bacteria had officially been declared dead, allowed revival of the NET-associated microbes (57). Indeed, we found that bacteria bound to PMA-induced NETs are alive, as determined by live/dead staining (18). The report of a patient with chronic granulomatous disease (CGD) and Aspergillus infection who was rescued by gene therapy that restored the capacity to mount a respiratory burst and generate NETs has been considered proof of principle of the role of NETs in immune defense (58).…”

“…Chemokine receptors are necessary for integrin activation and signaling (10,17). Integrins generate signals that elicit NETosis in response to bacteria, and NETs are not produced when integrins are deficient, such as in leukocyte adhesion deficiency (18). l-Selectinmediated signaling was recently demonstrated to elicit NETs in vitro (18).…”

“…Integrins generate signals that elicit NETosis in response to bacteria, and NETs are not produced when integrins are deficient, such as in leukocyte adhesion deficiency (18). l-Selectinmediated signaling was recently demonstrated to elicit NETs in vitro (18). Notably, the initial description of NET formation elicited by IL-8 in vitro has not been uniformly confirmed (19).…”

“…Failure to remove these two N-terminal amino acids results in the inability to generate active enzyme and complete degradation of the serine proteases before mature neutrophils are formed (11,63,64). These patients are therefore completely devoid of all neutrophil serine proteases, including elastase, and hence incapable of generating NETs (11), except by saliva (18). Ironically, saliva is supposed to prevent periodontal disease, which is the hallmark of Papillon-Lefèvre syndrome, but saliva-generated NETs are clearly not sufficient.…”

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

“…In vivo observation of neutrophils revealed their presence in the dental plaque and that NET formation is detected in the oral biofilm, the saliva, and also the crevicular exudate (155,197,(380)(381)(382). Due to the large quantity of bacteria present dispersed throughout the gingival crevice, phagocytosis is an ineffective means for bacterial control, therefore NETs could serve as a more effective strategy for neutrophils to respond to infection (197).…”