Artículo
Key role of toll-like receptor 2 in the inflammatory response and major histocompatibility complex class ii downregulation in Brucella abortus-infected alveolar macrophages
Ferrero, Mariana Cristina
; Hielpos, María Soledad
; Carvalho, Natalia B.; Barrionuevo, Paula
; Corsetti, Patricia P.; Giambartolomei, Guillermo Hernan
; Oliveira, Sergio C.; Baldi, Pablo Cesar
Fecha de publicación:
02/2014
Editorial:
American Society for Microbiology
Revista:
Infection and Immunity
ISSN:
0019-9567
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Alveolar macrophages (AM) seem to constitute the main cellular target of inhaled brucellae. Here, we show that Brucella abortus invades and replicates in murine AM without inducing cytotoxicity. B. abortus infection induced a statistically significant increase of tumor necrosis factor alpha (TNF-α), CXCL1 or keratinocyte chemoattractant (KC), interleukin-1β (IL-1β), IL-6, and IL-12 in AM from C57BL/6 mice and BALB/c mice, but these responses were generally weaker and/or delayed compared to those elicited in peritoneal macrophages. Studies using knockout mice for TLR2, TLR4, and TLR9 revealed that TNF-α and KC responses were mediated by TLR2 recognition. Brucella infection reduced in a multiplicity of infection-dependent manner the expression of major histocompatibility complex class II (MHC-II) molecules induced by gamma interferon (IFN-γ) in AM. The same phenomenon was induced by incubation with heat-killed B. abortus (HKBA) or the lipidated form of the 19-kDa outer membrane protein of Brucella (L-Omp19), and it was shown to be mediated by TLR2 recognition. In contrast, no significant downregulation of MHC-II was induced by either unlipidated Omp19 or Brucella LPS. In a functional assay, treatment of AM with either L-Omp19 or HKBA reduced the MHC-II-restricted presentation of OVA peptides to specific T cells. One week after intratracheal infection, viable B. abortus was detected in AM from both wild-type and TLR2 KO mice, but CFU counts were higher in the latter. These results suggest that B. abortus survives in AM after inhalatory infection in spite of a certain degree of immune control exerted by the TLR2-mediated inflammatory response. Both the modest nature of the latter and the modulation of MHC-II expression by the bacterium may contribute to such survival.
Palabras clave:
Brucella Abortus
,
Alveolar Macrophages
,
Tlr2
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IDEHU)
Articulos de INST.DE EST.DE LA INMUNIDAD HUMORAL PROF.R.A.MARGNI
Articulos de INST.DE EST.DE LA INMUNIDAD HUMORAL PROF.R.A.MARGNI
Articulos(INIGEM)
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Citación
Ferrero, Mariana Cristina; Hielpos, María Soledad; Carvalho, Natalia B.; Barrionuevo, Paula; Corsetti, Patricia P.; et al.; Key role of toll-like receptor 2 in the inflammatory response and major histocompatibility complex class ii downregulation in Brucella abortus-infected alveolar macrophages; American Society for Microbiology; Infection and Immunity; 82; 2; 2-2014; 626-639
Compartir
Altmétricas