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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

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.

Publisher's Note: There is an Inside Blood Commentary on this article in this issue.

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 LewisX 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 LewisX 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.

  • Submitted April 17, 2015.
  • Accepted July 20, 2015.
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