AUTHOR=Pesce Viglietti Ayelén Ivana , Sviercz Franco Agustín , López Cinthya Alicia Marcela , Freiberger Rosa Nicole , Quarleri Jorge , Delpino María Victoria 

TITLE=Proinflammatory Microenvironment During Kingella kingae Infection Modulates Osteoclastogenesis

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.757827

DOI=10.3389/fimmu.2021.757827

ISSN=1664-3224

ABSTRACT=<p><italic>Kingella kingae</italic> is an emerging pathogen that causes septic arthritis, osteomyelitis, and bacteremia in children from 6 to 48 months of age. The presence of bacteria within or near the bone is associated with an inflammatory process that results in osteolysis, but the underlying pathogenic mechanisms involved are largely unknown. To determine the link between <italic>K. kingae</italic> and bone loss, we have assessed whether infection <italic>per se</italic> or through the genesis of a pro-inflammatory microenvironment can promote osteoclastogenesis. For that purpose, we examined both the direct effect of <italic>K. kingae</italic> and the immune-mediated mechanism involved in <italic>K. kingae</italic>-infected macrophage-induced osteoclastogenesis. Our results indicate that osteoclastogenesis is stimulated by <italic>K. kingae</italic> infection directly and indirectly by fueling a potent pro-inflammatory response that drives macrophages to undergo functional osteoclasts <italic>via</italic> TNF-α and IL-1β induction. Such osteoclastogenic capability of <italic>K. kingae</italic> is counteracted by their outer membrane vesicles (OMV) in a concentration-dependent manner. In conclusion, this model allowed elucidating the interplay between the <italic>K. kingae</italic> and their OMV to modulate osteoclastogenesis from exposed macrophages, thus contributing to the modulation in joint and bone damage.</p>