INVESTIGADORES
FOSSATI Carlos Alberto
artículos
Título:
Proinflammatory response of human osteoblastic cell lines and osteoblast-monocyte interaction upon infection with Brucella spp
Autor/es:
DELPINO MV; FOSSATI CA; BALDI PC,
Revista:
INFECTION AND IMMUNITY
Editorial:
AMER SOC MICROBIOLOGY
Referencias:
Año: 2009 vol. 77 p. 984 - 995
ISSN:
0019-9567
Resumen:
The ability of Brucella spp. to infect human osteoblasts and the cytokine response of these cells to infection
were investigated in vitro. Brucella abortus, B. suis, B. melitensis, and B. canis were able to infect the SaOS-2 and
MG-63 osteoblastic cell lines, and the first three species exhibited intracellular replication. B. abortus internalization
was not significantly affected by pretreatment of cells with cytochalasin D but was inhibited up to
92% by colchicine. A virB10 mutant of B. abortus could infect but not replicate within osteoblasts, suggesting
a role for the type IV secretion system in intracellular survival. Infected osteoblasts produced low levels of
chemokines (interleukin-8 [IL-8] and macrophage chemoattractant protein 1 [MCP-1]) and did not produce
proinflammatory cytokines (IL-1_, IL-6, and tumor necrosis factor alpha [TNF-_]). However, osteoblasts
stimulated with culture supernatants from Brucella-infected human monocytes (THP-1 cell line) produced
chemokines at levels 12-fold (MCP-1) to 17-fold (IL-8) higher than those of infected osteoblasts and also
produced IL-6. In the inverse experiment, culture supernatants from Brucella-infected osteoblasts induced the
production of IL-8, IL-1_, IL-6, and TNF-_ by THP-1 cells. The induction of TNF-_ and IL-1_ was largely due
to granulocyte-macrophage colony-stimulating factor produced by infected osteoblasts, as demonstrated by
inhibition with a specific neutralizing antibody. This study shows that Brucella can invade and replicate within
human osteoblastic cell lines, which can directly and indirectly mount a proinflammatory response. Both
phenomena may have a role in the chronic inflammation and bone and joint destruction observed in osteoarticular brucellosis