INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The activation of human brain microvascular endothelial cells by Brucella abortus-infected glial cells is mediated by IL-1β
Autor/es:
MIRAGLIA M. C., SILVA COSTA FRANCO M. M., RODRIGUEZ A. M., BARRIONUEVO P., DELPINO M. V., OLIVEIRA S. C., GIAMBARTOLOMEI, G. H
Reunión:
Congreso; LXII Reunión Científica de la Sociedad Argentina de Inmunología; 2014
Resumen:
B. abortus
can interact with human brain microvascular endothelial cells (HBMEC) and gain
access to the central nervous system consequently eliciting the inflammatory
pathology named neurobrucellosis. We have recently demonstrated that although B.
abortus can infect HBMEC, the indirect effect of glial cells infected with
the bacterium is more effective in activating the endothelium. Both, TNF-α and
IL-1β secreted by glial cells were reported to mediate HBMEC activation. Since
we have demonstrated that these cytokines were secreted by B. abortus-infected
astrocytes and microglia, we decided to investigate their role in activation of
HBMEC (cytokine secretion ad expression of adhesion molecules). Supernatants
from B. abortus-infected astrocytes and microglia induced the production
of IL-6, IL-8 and MCP-1 and up-regulated the expression of ICAM-1 on HBMEC.
When HBMEC were stimulated with culture supernatants of B. abortus-infected
astrocytes and microglia from CASP-1 and ASC KO mice (unable to produce IL-1β),
cytokine production and ICAM-1 expression was completely inhibited (p<0.001
vs. WT). Neutralization of TNF-α had no effect on glial cells-induced HBMEC
activation. The involvement of ASC in glial cells-induced HBMEC activation
indicated that IL-1β secretion proceeds via the inflammasome. The activation of
this complex requires a first signal which is usually triggered via TLR.
Secretion of IL-6, IL-8 and MCP-1 and ICAM-1 expression was completely
inhibited (p<0.001) when HBMEC were stimulated with culture supernatants of B.
abortus-infected astrocytes and microglia from MAL/TIRAP and TLR2 KO mice.
On the contrary supernatants from TLR4 or TLR6 glial cells induced the same
level of activation of HBMEC than supernatants from wild type cells. Our results
demonstrate that glial cells-secreted IL-1β induced by the infection of B.
abortus mediates activation of HBMEC. They also show that TLR2 and ASC/CASP
mediate IL-1β production in B. abortus-infected glial cells.