STAPHYLOCOCCUS AUREUS PROTEIN A INTERACTION WITH TNFR1 CONTRIBUTES TO OSTEOCLASTOGENESIS

ANDREA MENDOZA BERTELLI; M. VICTORIA DELPINO; MARIÁNGELES NOTO LLANA; DANIEL SORDELLI; MARISA I. GOMEZ

Buenos Aires

Congreso; Imeeting LASID 2015; 2015

Staphylococcus aureus is one of the most prevalent pathogens that cause osteomyelitis in adults. S. aureus protein A (SpA) is a virulence factor that interacts with the TNF receptor 1 (TNFR1) and mimics TNF-α signaling. Given the importance of TNF-α in the induction of osteoclast differentiation and the regulation of bone metabolism, we hypothesize that SpA may contribute to increase osteoclastogenesis. Bone marrow derived macrophages (BMM) were stimulated with SpA, S. aureus or the isogenic spa- mutant during 9 days and multinucleated cells positive for the tartrate resistant acid phosphatase (TRAP) were enumerated. A significant increase in the number of cells differentiated to osteoclasts in response to SpA and S. aureus was observed compared with cells stimulated with the spa- mutant. Using BMM from TNFR1-/- mice and a mutant that is not able to signal through EGFR (L17A) we demonstrated that SpA induces osteoclastogenesis via TNFR1 and EGFR mediated signaling. Osteoclasts differentiated in response to S. aureus were able to resorb dentine whereas cells stimulated in the presence of the spa- mutant did not form resorption pits. Interestingly, S. aureus did not induce resorption pits on osteoclasts from TNFR1-/- mice indicating a role for TNFR1 signaling during osteoclastogenesis. Moreover, we demonstrated that SpA significantly contributes to osteoclastogenesis, resorbing MMP-9 activity and bone damage in vivo using an experimental model of osteomyelitis. These results suggest that S. aureus protein A significantly contributes to osteoclast differentiation and it may play a critical role in the increased bone resorption that occurs during osteomyelitis.