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Artículo

Brucella abortus-infected macrophages modulate T lymphocytes to promote osteoclastogenesis via IL-17

Giambartolomei, Guillermo HernanIcon ; Scian, RominaIcon ; Acosta Rodriguez, Eva VirginiaIcon ; Fossati, Carlos AlbertoIcon ; Delpino, María VictoriaIcon
Fecha de publicación: 09/2012
Editorial: American Society of Investigative Pathology
Revista: American Journal Of Pathology
ISSN: 0002-9440
e-ISSN: 1525-2191
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Enfermedades Infecciosas

Resumen

The pathogenic mechanisms of bone loss caused by Brucella species have not been completely deciphered. Although T lymphocytes (LTs) are considered important to control infection, the mechanism of Brucella-induced T-cell responses to immunopathological features is not known. We present in vitro and in vivo evidence showing that Brucella abortusinduced inflammatory response leads to the activation of LTs, which further promote osteoclastogenesis. Pre-activated murine LTs treated with culture supernatant from macrophages infected with B. abortus induced bone marrowderived monocytes (BMMs) to undergo osteoclastogenesis. Furthermore, osteoclastogenesis was mediated by CD4 + T cells. Although B. abortusactivated T cells actively secreted the pro-osteoclastogenic cytokines RANKL and IL-17, osteoclastogenesis depended on IL-17, because osteoclast generation induced by Brucella-activated T cells was completely abrogated when these cells were cultured with BMMs from IL-17 receptor knockout mice. Neutralization experiments indicated that IL-6, generated by Brucella infection, induced the production of pro-osteoclastogenic IL-17 from LTs. By using BMMs from tumor necrosis factor receptor p55 knockout mice, we also demonstrated that IL-17 indirectly induced osteoclastogenesis through the induction of tumor necrosis factor-α from osteoclast precursors. Finally, extensive and widespread osteoclastogenesis was observed in the knee joints of mice injected with Brucella-activated T cells. Our results indicate that activated T cells, elicited by B. abortusinfected macrophages and influenced by the inflammatory milieu, promote the generation of osteoclasts, leading to bone loss. © 2012 American Society for Investigative Pathology.
Palabras clave: Brucella Abortus , Osteoclastogenesis , T Lymphocyte , Il-17
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/55150
URL: https://www.sciencedirect.com/science/article/pii/S0002944012004348
DOI: http://dx.doi.org/10.1016/j.ajpath.2012.05.029
Colecciones
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos(INIGEM)
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Citación
Giambartolomei, Guillermo Hernan; Scian, Romina; Acosta Rodriguez, Eva Virginia; Fossati, Carlos Alberto; Delpino, María Victoria; Brucella abortus-infected macrophages modulate T lymphocytes to promote osteoclastogenesis via IL-17; American Society of Investigative Pathology; American Journal Of Pathology; 181; 3; 9-2012; 887-896
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