Proinflammatory Microenvironment During Kingella kingae Infection Modulates Osteoclastogenesis

• DOI: 10.3389/fimmu.2021.757827
• Publication Date: 2021-12-02T10:36:12Z
• Authors: Ayelén Ivana Pesc...; Franco Agustín Sv...; Cinthya Alicia Ma...; Rosa Nicole Freib...; Jorge Quarleri; María Victoria De...
• Keywords: Neisseriaceae Infections; Osteoclasts; Kingella kingae; Osteolysis; Mice; https://purl.org/becyt/ford/3.3; Osteogenesis; Diagnosis and Treatment of Spinal Infections; Internal medicine; 0303 health sciences; Proinflammatory cytokine; 3. Good health; Chemistry; Cellular Microenvironment; OSTEOCLASTOGENESIS AND BONE LOSS; IL-1β; osteoclastogenesis and bone loss; Medicine; Osteoclast; Receptor; Immunology; Infection Risk Factors; Microbiology; Cell Line; 03 medical and health sciences; Diagnosis and Treatment of Prosthetic Joint Infections; INFLAMMATION; Rheumatology; IL-1Β; TNF-Α; Health Sciences; Animals; Humans; https://purl.org/becyt/ford/3; KINGELLA KINGAE; Biology; Autoinflammatory Bone Disorders; Inflammation; Macrophages; FOS: Clinical medicine; Arthritis; RC581-607; RAW 264.7 Cells; inflammation; TNF-α; FOS: Biological sciences; Dentistry; Septic arthritis; Surgery; Immunologic diseases. Allergy

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.