INVESTIGADORES
GIAMBARTOLOMEI Guillermo Hernan
artículos
Título:
Brucella abortus invade osteoblasts inhibiting bone formation
Autor/es:
SCIAN R, BARRIONUEVO P, FOSSATI CA, GIAMBARTOLOMEI GH, DELPINO MV.
Revista:
INFECTION AND IMMUNITY
Editorial:
AMER SOC MICROBIOLOGY
Referencias:
Lugar: Washington; Año: 2012 vol. 80 p. 2333 - 2345
ISSN:
0019-9567
Resumen:
Osteoarticular brucellosis is the most common presentation of the active disease
in humans. 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 infectious conditions. In this article, we
describe immune mechanisms whereby Brucella abortus may invade and replicate
within osteoblasts, inducing apoptosis, inhibiting mineral and organic matrix
deposition, and inducing upregulation 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. In addition, 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 demonstrated that supernatants from B.
abortus-infected macrophages may also mediate osteoblast apoptosis and inhibit
osteoblast function in a process that is dependent on the presence of tumor
necrosis factor alpha (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 complications of
brucellosis.