Neutrophils modulate natural killer-mediated osteoclastogenesis during Aggregatibacteractinomycetemcomitans (JP2 clone) infection

Bshara Halloun; Koren Hashai; Noy Pinto; Nadav Musai; Yehuda Klein; David Polak

doi:10.1016/j.isci.2023.106430

Neutrophils modulate natural killer-mediated osteoclastogenesis during Aggregatibacteractinomycetemcomitans (JP2 clone) infection

iScience. 2023 Mar 16;26(8):106430. doi: 10.1016/j.isci.2023.106430. eCollection 2023 Aug 18.

Authors

Bshara Halloun¹, Koren Hashai², Noy Pinto³, Nadav Musai², Yehuda Klein³, David Polak²

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Hebrew University-Hadassah, Jerusalem, Israel.
² Department of Periodontology, Hebrew University-Hadassah Faculty of Dental Medicine, Israel.
³ Department of Orthodontics, Hebrew University-Hadassah Faculty of Dental Medicine, Israel.

Abstract

The study investigates the interplay of neutrophils and natural-killer cells (NK) in mediating osseoresorption during infection of molar-incisor-pattern-periodontitis (MIPP). Human neutrophils from periodontally healthy and MIPP patients were inoculated with the periopathogen Aggregatibacter-actinomycetemcomitans (JP2) and their supernatants were exposed to NK to study their function and osteoclastogenesis promotion. A mouse MIPP model was used to compare disease progression following NK versus neutrophils depletion. The exposure of primary NK to supernatants of neutrophils inoculated with JP2 led to NK cell arrest and activation with enhanced osteoprotegerin expression. Incubation of monocytes with NK led to osteoclastogenesis, whereas 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.

Keywords: Bacteriology; Immunology; Microbiology.