IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
artículos
Título:
Brucella abortus Induces the Secretion of Proinflammatory Mediators from Glial Cells Leading to astrocyte apoptosis
Autor/es:
CLARA GARCÍA SAMARTINO; M.VICTORIA DELPINO; CLARA POTT GODOY; MARÍA SILVIA DI GENARO; KARINA PASQUEVICH; ASTRID ZWERDLING; PAULA BARRIONUEVO; PATRICIA MATHIEU; JULIANA CASSATARO; FERNANDO J. PITOSSI; GILLERMO H GIAMBARTOLOMEI
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 presentBrucella results in an inflammatory disorder
called neurobrucellosis. In this study we present
in vivo and in vitro evidence 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. abortusand in vitro evidence 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. abortusB. abortus
(HKBA) or outer membrane protein 19 (Omp19), a
B. abortus lipoprotein model, induced astrogliosis in
mouse striatum. Moreover, infection of astrocytes
and microglia with B. abortus induced the secretion
of interleukin (IL)6, IL-1, tumor necrosis factor
(TNF)-, macrophage chemoattractant protein1,
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. Indeed, 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- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)B. abortus infection induced astrocyte,
but not microglia, apoptosis. Indeed, 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- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)lipoprotein model, induced astrogliosis in
mouse striatum. Moreover, infection of astrocytes
and microglia with B. abortus induced the secretion
of interleukin (IL)6, IL-1, tumor necrosis factor
(TNF)-, macrophage chemoattractant protein1,
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. Indeed, 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- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)B. abortus infection induced astrocyte,
but not microglia, apoptosis. Indeed, 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- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)B. abortus induced the secretion
of interleukin (IL)6, IL-1, tumor necrosis factor
(TNF)-, macrophage chemoattractant protein1,
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. Indeed, 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- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)B. abortus infection induced astrocyte,
but not microglia, apoptosis. Indeed, 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- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)6, IL-1, tumor necrosis factor
(TNF)-, macrophage chemoattractant protein1,
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. Indeed, 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- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)B. abortus infection induced astrocyte,
but not microglia, apoptosis. Indeed, 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- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503), macrophage chemoattractant protein1,
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. Indeed, 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- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)B. abortus infection induced astrocyte,
but not microglia, apoptosis. Indeed, 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- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)/ mice or when the general caspase inhibitor
Z-VAD-FMK was added to cultures. Hence, TNF- signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503) signaling
via TNF receptor (TNFR) 1 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. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)Brucella lipoproteins
could be key virulence factors in neurobrucellosis
and that astrogliosis might contribute to neurobrucellosis
pathogenesis. (Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)(Am J Pathol 2010, 176:13231338;
DOI: 10.2353/ajpath.2010.090503)