Proinflammatory Microenvironment During Kingella kingae Infection Modulates Osteoclastogenesis

PESCE VIGLIETTI, AYELÉN IVANA; SVIERCZ, FRANCO AGUSTÍN; LÓPEZ, CINTHYA ALICIA MARCELA; FREIBERGER, ROSA NICOLE; QUARLERI, JORGE; DELPINO, MARÍA VICTORIA

Frontiers in Immunology

Frontiers

Año: 2021 vol. 12

Kingella kingae is an emerging pathogen that causes septic arthritis, osteomyelitis, andbacteremia in children from 6 to 48 months of age. The presence of bacteria within or nearthe bone is associated with an inflammatory process that results in osteolysis, but theunderlying pathogenic mechanisms involved are largely unknown. To determine the linkbetween K. kingae and bone loss, we have assessed whether infection per se or throughthe genesis of a pro-inflammatory microenvironment can promote osteoclastogenesis.For that purpose, we examined both the direct effect of K. kingae and the immunemediated mechanism involved in K. kingae-infected macrophage-inducedosteoclastogenesis. Our results indicate that osteoclastogenesis is stimulated by K.kingae infection directly and indirectly by fueling a potent pro-inflammatory responsethat drives macrophages to undergo functional osteoclasts via TNF-a and IL-1b induction.Such osteoclastogenic capability of K. kingae is counteracted by their outer membranevesicles (OMV) in a concentration-dependent manner. In conclusion, this model allowedelucidating the interplay between the K. kingae and their OMV to modulateosteoclastogenesis from exposed macrophages, thus contributing to the modulation injoint and bone damage.