INVESTIGADORES
DELPINO Maria Victoria
congresos y reuniones científicas
Título:
T cell-mediated regulation of Brucella abortus-induced osteoclastogenesis. Scian
Autor/es:
SCIAN ROMINA; BALDI PABLO C; FOSSATI CARLOS A; GIAMBARTOLOMEI GUILLERMO; DELPINO M. VICTORIA
Lugar:
Buenos Aires, Argentina
Reunión:
Congreso; 1º Congreso Franco-Argentino de Inmunología (FAIC) y LVIII Reunión Anual de la Sociedad Argentina de Inmunología.; 2010
Resumen:
Osteoarticular complications are common in human brucellosis, but the pathogenic mechanisms involved are largely unknown.  We have previously shown that Brucella-infected macrophages not only produce pro-inflammatory cytokines, that may eventually produce bone damage, but they can also differentiate to osteoclasts (cells implicated in bone resorption). T lymphocytes can modulate osteoclastogenesis, inhibiting it or accelerating it, depending on the factors secreted. Thus, we decided to investigate the modulatory role of T lymphocytes in the Brucella-induced differentiation of macrophages into osteoclasts. Supernatants from Brucella-infected murine macrophages were used to stimulate T lymphocytes (LT) pre-activated with anti-CD3å antibodies. After 24 h of incubation, medium was replaced and LT were cultured for another 24 h before harvesting supernatants to determine by ELISA the levels of RANKL and IL-17 (inductors of osteoclastogenesis) and IFN-ã (inhibitor of osteoclastogenesis), or were co-cultured with bone marrow cells in the presence of M-CSF to determine their capacity to induce or inhibit osteoclastogenesis. As compared with LT stimulated with supernatants from uninfected macrophages, LT stimulated with supernatants from infected macrophages secreted higher levels of RANKL (2450±122 vs. 144±87 pg/ml) and IL-17 (720±28 vs. 88±12 pg/ml), while IFN-ã levels were lower than those secreted by unstimulated cells (560±45 vs. 2100±122 pg/ml). This balance of cytokines resulted in the induction of osteoclastogenesis, as indicated by the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells with up-regulated vitronectin receptor and also by the capacity of these cells to resorb dentine. These results indicate that LT are involved in bone damage in osteoarticular brucellosis through the pathological induction of osteoclastogenesis