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

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 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 NET release independent of elastase and NADPH-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 PMA. Furthermore, saliva/sialyl lewis(X) mediated signaling enhanced intracellular killing of bacteria by neutrophils. Saliva from patients with aphthous ulcers and Behçet's disease prone to oral ulcers, failed to induce NETosis, but for different reasons, demonstrating that disordered homeostasis in the oral cavity may result in deficient saliva-mediated NETosis.