SORDELLI Daniel Oscar
congresos y reuniones científicas
Staphylococcus aureus protein A interaction with TNFR1contributes to osteoclastogenesis and may play a critical role in the increase of bone resorption.
MENDOZA BERTELLI A; DELPINO MV; NOTO LLANA M; SORDELLI DO; GOMEZ MI
Congreso; LXIII Reunión anual de la Sociedad Argentina de Inmunologia SAI; 2015
SOCIEDAD ARGENTINA DE INMUNOLOGIA
Staphylococcus aureus is one of the most prevalent pathogens that cause osteomyelitis inadults. S. aureus protein A (SpA) is a virulence factor that interactswith 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 ofbone metabolism, we hypothesize that SpA may contribute to increaseosteoclastogenesis. Bone marrow derived macrophages (BMM) were stimulated withSpA, S. aureus or the isogenic spa- mutant during 9 days andmultinucleated cells positive for the tartrate resistant acid phosphatase(TRAP) were enumerated. A significant increase in the number of cells differentiatedto osteoclasts in response to SpA and S. aureus was observed comparedwith cells stimulated with the spa- mutant. Using BMM from TNFR1-/- miceand a mutant that is not able to signal through EGFR (L17A) we demonstratedthat SpA induces osteoclastogenesis via TNFR1 and EGFR mediated signaling.Osteoclasts differentiated in response to S. aureus were able to resorbdentine whereas cells stimulated in the presence of the spa- mutant didnot form resorption pits. Interestingly, S. aureus did not induce resorptionpits on osteoclasts from TNFR1-/- mice indicating a role for TNFR1 signalingduring osteoclastogenesis. Moreover, we demonstrated that SpA significantlycontributes to osteoclastogenesis, resorbing MMP-9 activity and bone damage invivo using an experimental model of osteomyelitis. These results suggestthat S. aureus protein A significantly contributes to osteoclastdifferentiation and it may play a critical role in the increased boneresorption that occurs during osteomyelitis.