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

Tirthankar Mohanty, Jonathan Sjögren, Fredrik Kahn, Anas H A Abu-Humaidan, Niels Fisker, Kristian Assing, Matthias Mörgelin, Anders A Bengtsson, Niels Borregaard, Ole E Sørensen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had released neutrophil extracellular traps (undergone NETosis) in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl Lewis(X) present on salival mucins to l-selectin on neutrophils. This led to rapid loss of nuclear membrane and intracellular release of granule proteins with subsequent neutrophil extracellular trap (NET) release independent of elastase and reduced NAD phosphate-oxidase activation. The saliva-induced NETs were more DNase-resistant and had higher capacity to bind and kill bacteria than NETs induced by bacteria or by phorbol-myristate acetate. Furthermore, saliva/sialyl Lewis(X) mediated signaling enhanced intracellular killing of bacteria by neutrophils. Saliva from patients with aphthous ulcers and Behçet disease prone to oral ulcers failed to induce NETosis, but for different reasons it demonstrated that disordered homeostasis in the oral cavity may result in deficient saliva-mediated NETosis.

Original languageEnglish
JournalBlood
Volume126
Issue number18
Pages (from-to)2128-37
Number of pages10
ISSN0006-4971
DOIs
Publication statusPublished - 2015

Fingerprint

Dive into the research topics of 'A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa'. Together they form a unique fingerprint.

Cite this