Abstract
Kingella kingae 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 K. kingae and bone loss, we have assessed whether infection per se or through the genesis of a pro-inflammatory microenvironment can promote osteoclastogenesis. For that purpose, we examined both the direct effect of K. kingae and the immune-mediated mechanism involved in K. kingae-infected macrophage-induced osteoclastogenesis. Our results indicate that osteoclastogenesis is stimulated by K. kingae infection directly and indirectly by fueling a potent pro-inflammatory response that drives macrophages to undergo functional osteoclasts via TNF-α and IL-1β induction. Such osteoclastogenic capability of K. kingae is counteracted by their outer membrane vesicles (OMV) in a concentration-dependent manner. In conclusion, this model allowed elucidating the interplay between the K. kingae and their OMV to modulate osteoclastogenesis from exposed macrophages, thus contributing to the modulation in joint and bone damage.
Highlights
Kingella kingae is a common etiology agent of septic arthritis, osteomyelitis, and bacteremia in children from 6 to 48 months of age
The production of IL-6, TNF-a, IL-1b, and receptor activator of NF-kB ligand (RANKL) in culture supernatants from THP-1 monocytes in response to K. kingae infection was examined
Infection of human monocytes with K. kingae performed at multiplicity of infection (MOI) of 1 and 10 elicited the secretion of IL-6, TNF-a, and IL-1b at 24 h post-infection in an inoculum-dependent manner (Figure 1A)
Summary
Kingella kingae is a common etiology agent of septic arthritis, osteomyelitis, and bacteremia in children from 6 to 48 months of age. This bacteria is an emerging pediatric pathogen characterized by asymptomatic pharyngeal colonization that could be followed by bacterial translocation across the pharyngeal epithelial barrier with dissemination to distant locations, including infective endocarditis, bacteremia, septic arthritis, and osteomyelitis [1, 2]. The presence of bacteria within or near the bone is associated with an inflammatory process that results in osteolysis, and K. kingae appears not to be an exception [4,5,6]
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