CD4+ T cell-derived IL-10 promotes Brucella abortus persistence via modulation of macrophage function.
PLoS Pathog
; 9(6): e1003454, 2013.
Article
en En
| MEDLINE
| ID: mdl-23818855
ABSTRACT
Evasion of host immune responses is a prerequisite for chronic bacterial diseases; however, the underlying mechanisms are not fully understood. Here, we show that the persistent intracellular pathogen Brucella abortus prevents immune activation of macrophages by inducing CD4(+)CD25(+) T cells to produce the anti-inflammatory cytokine interleukin-10 (IL-10) early during infection. IL-10 receptor (IL-10R) blockage in macrophages resulted in significantly higher NF-kB activation as well as decreased bacterial intracellular survival associated with an inability of B. abortus to escape the late endosome compartment in vitro. Moreover, either a lack of IL-10 production by T cells or a lack of macrophage responsiveness to this cytokine resulted in an increased ability of mice to control B. abortus infection, while inducing elevated production of pro-inflammatory cytokines, which led to severe pathology in liver and spleen of infected mice. Collectively, our results suggest that early IL-10 production by CD25(+)CD4(+) T cells modulates macrophage function and contributes to an initial balance between pro-inflammatory and anti-inflammatory cytokines that is beneficial to the pathogen, thereby promoting enhanced bacterial survival and persistent infection.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Brucella abortus
/
Brucelosis
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Linfocitos T CD4-Positivos
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Interleucina-10
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Viabilidad Microbiana
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Activación de Macrófagos
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Macrófagos
Límite:
Animals
Idioma:
En
Revista:
PLoS Pathog
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos