Neutrophils Modulate Natural Killer-Mediated Osteoclastogenesis During <i>Aggregatibacter actinomycetemcomitans</i> (JP2 Clone) Infection

The study investigates the interplay of neutrophils and NK in mediating osseoresorption during infection of molar-incisor-pattern-periodontitis (MIPP). Human neutrophils from periodontally healthy and MIPP patients were inoculated with JP2 and their supernatants were exposed to NK cells to study their function and osteoclastogenesis promotion. A mouse MIPP model was used to compared disease progression following NK depletion versus neutrophils depletion and WT. The exposure of primary NK to supernatants of neutrophils inoculated with JP2 led to NK cell arrest and activation, along with enhanced expression of osteoprotegerin. Incubation of monocytes with NK led to osteoclastogenesis, while NK that were pre-exposed to healthy neutrophil supernatant showed reduced osteoclastogenesis. In mice, NK depletion led to the similar bone phenotype as the neutrophil's depletion highlighting their role on osseoprotection. The present study portrays a key crosstalk between neutrophils and NK cells during JP2 infection as a central mechanism that regulates bone loss.Funding Information: The study was self-funded. Declaration of Interests: We do not have commercial or other associations that might pose a conflict of interest. Ethics Approval Statement: The study was approved by the institutional Helsinki review board (Hadassah Medical Center approval number 0514-13-HMO). All subjects signed their inform consent before participation in the study.