Brucella abortus Invasion of Osteoblasts Inhibits Bone Formation

SCIAN ROMINA; BARRIONUEVO PAULA; FOSSATI CARLOS A; GIAMBARTOLOMEI GUILLERMO; DELPINO M VICTORIA

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2012 vol. 80 p. 2333 - 2345

0019-9567

Osteoarticular brucellosis is the most common presentation of human active disease. Loss of bone is a serious complication of localized bacterial infection of bones or the adjacent tissue, and brucellosis proved not to be the exception. The skeleton is a dynamic organ system which is constantly remodeled. Osteoblasts are responsible for the deposition of bone matrix and are thought to facilitate the calcification and mineralization of the bone matrix, and their function could be altered under infection conditions. In this manuscript, we described immune mechanisms whereby Brucella abortus may invade and replicate within osteoblasts inducing apoptosis, inhibiting mineral and organic matrix deposition, and inducing up-regulation of RANKL expression. Additionally, all of these mechanisms contributed in different ways to bone loss. These processes implicate the activation of signaling pathways (mitogen-activated protein kinases [MAPK] and caspases) involved in cytokine secretion, expression of activating molecules and cell death of osteoblasts. Besides, considering the relevance of macrophages in intracellular Brucella survival, and proinflammatory cytokine secretion in response to infection, we also investigated the role of these cells as modulators of osteoblast survival, differentiation and function. We demonstrate that, supernatants from B. abortus infected macrophages may also mediate osteoblast apoptosis, and inhibit their function in a process that is depended on the presence of TNF-α. These results indicate that B. abortus may directly and indirectly harm osteoblast function contributing to the bone and joint destruction observed in patients with osteoarticular complicacions of brucellosis.