INVESTIGADORES
GIAMBARTOLOMEI Guillermo Hernan
artículos
Título:
Brucella abortus induces the secretion of pro-inflammatory mediators from glial cells leading to astrocyte apoptosis.
Autor/es:
GARCIA SAMARTINO C., DELPINO M. V., POTT GODOY C., DI GENARO M. S., PASQUEVICH K. A., ZWERDLING A., BARRIONUEVO P., MATHIEU P., CASSATARO J., PITOSSI F., GIAMBARTOLOMEI G. H.
Revista:
AMERICAN JOURNAL OF PATHOLOGY
Editorial:
AMER SOC INVESTIGATIVE PATHOLOGY, INC
Referencias:
Año: 2010 vol. 176 p. 1323 - 1338
ISSN:
0002-9440
Resumen:
Central nervous system (CNS) invasion by bacteria of the genus Brucella results in an inflammatory disorder called neurobrucellosis. In this study we present in vivo and in vitro evidence showing that B. abortus and its lipoproteins activate the innate immunity of the CNS, eliciting an inflammatory response that leads to astrogliosis, a characteristic feature of neurobrucellosis. Intracranial injection of heat-killed B. abortus (HKBA) or outer membrane protein 19 (Omp19), a B. abortus lipoprotein model, induced astrogliosis in mouse striatum. Infection of astrocyte and microglia with B. abortus induced the secretion of interleukin (IL)-6, IL-1b, tumor necrosis factor (TNF)-a, macrophage chemoattractant protein (MCP)-1 and KC (CXCL1). HKBA also induced these inflammatory mediators, suggesting the involvement of a structural component of the bacterium. Accordingly, Omp19 induced the same cytokine and chemokine secretion pattern. B. abortus infection induced astrocyte, but not microglia, apoptosis. HKBA and Omp19 elicited not only astrocyte apoptosis but also proliferation, two features observed during astrogliosis. Apoptosis induced by HKBA and L-Omp19 was completely suppressed in cells of TNF receptor p55-/- mice or when the general caspase inhibitor Z-VAD-FMK was added to cultures. Hence, TNF-á signaling via TNFR1 through the coupling of caspases determines apoptosis. Our results provide proof of the principle that Brucella lipoproteins could be key virulence factors in neurobrucellosis, and that astrogliosis might contribute to neurobrucellosis pathogenesis.