Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier

Tissue-specific cues are critical for homeostasis at mucosal barriers. Here, we report that the clotting factor fibrin is a critical regulator of neutrophil function at the oral mucosal barrier. We demonstrate that commensal microbiota trigger extravascular fibrin deposition in the oral mucosa. Fibrin engages neutrophils through the alpha(M)beta(2) integrin receptor and activates effector functions, including the production of reactive oxygen species and neutrophil extracellular trap formation. These immune-protective neutrophil functions become tissue damaging in the context of impaired plasmin-mediated fibrinolysis in mice and humans. Concordantly, genetic polymorphisms in PLG, encoding plasminogen, are associated with common forms of periodontal disease. Thus, fibrin is a critical regulator of neutrophil effector function, and fibrin-neutrophil engagement may be a pathogenic instigator for a prevalent mucosal disease.

Automated summary

Tissue-specific cues, particularly fibrin, play a critical role in regulating neutrophil function at mucosal barriers, with commensal microbiota triggering extravascular fibrin deposition. Fibrin engages neutrophils through integrin receptors and activates immune-protective functions, but impaired fibrinolysis can lead to tissue damage. Polymorphisms in plasminogen gene are associated with periodontal disease, suggesting that fibrin-neutrophil engagement may contribute to mucosal diseases.