Staphylococcus aureus protein A interaction with TNFR1 contributes to osteoclastogenesis and may play a critical role in the increase of bone resorption.

ANDREA C. MENDOZA BERTELLI; M. VICTORIA DELPINO; MARIÁNGELES NOTO LLANA; DANIEL O. SORDELLI; MARISA GÓMEZ

Congreso; 53. LXIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI). 18-21 Noviembre de 2015.; 2015

Staphylococcus aureus protein A interaction with TNFR1 contributes toosteoclastogenesis and may play a critical role in the increase of boneresorption Andrea C. Mendoza Bertelli1, M. VictoriaDelpino2, Mariángeles Noto Llan1, Daniel O. Sordelli1, Marisa Gómez 1 1 IMPaM,UBA-CONICET 2 INIGEM,UBA-CONICET Abstract: Staphylococcus aureus is one of the most prevalent pathogensthat cause osteomyelitis in adults. S. aureus protein A (SpA) is a virulencefactor 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 andthe regulation of bone metabolism, we hypothesize that SpA may contribute toincrease osteoclastogenesis. Bone marrow derived macrophages (BMM) werestimulated with SpA, 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 cellsdifferentiated to osteoclasts in response to SpA and S. aureus was observedcompared with cells stimulated with the spa- mutant. Using BMM from TNFR1-/-mice and a mutant that is not able to signal through EGFR (L17A) wedemonstrated that SpA induces osteoclastogenesis via TNFR1 and EGFR mediatedsignaling. Osteoclasts differentiated in response to S. aureus were able toresorb dentine 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 suggest thatS. aureus protein A significantly contributes to osteoclast differentiation andit may play a critical role in the increased bone resorption that occurs duringosteomyelitis.