Essential role for IL-27 receptor signaling in prevention of Th1-mediated immunopathology during malaria infection.
J Immunol
; 185(4): 2482-92, 2010 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-20631310
ABSTRACT
Successful resolution of malaria infection requires induction of proinflammatory immune responses that facilitate parasite clearance; however, failure to regulate this inflammation leads to immune-mediated pathology. The pathways that maintain this immunological balance during malaria infection remain poorly defined. In this study, we demonstrate that IL-27R-deficient (WSX-1(-/-)) mice are highly susceptible to Plasmodium berghei NK65 infection, developing exacerbated Th1-mediated immune responses, which, despite highly efficient parasite clearance, lead directly to severe liver pathology. Depletion of CD4(+) T cells---but not CD8(+) T cells---prevented liver pathology in infected WSX-1(-/-) mice. Although WSX-1 signaling was required for optimal IL-10 production by CD4(+) T cells, administration of rIL-10 failed to ameliorate liver damage in WSX-1(-/-) mice, indicating that additional, IL-10-independent, protective pathways are modulated by IL-27R signaling during malaria infection. These data are the first to demonstrate the essential role of IL-27R signaling in regulating effector T cell function during malaria infection and reveal a novel pathway that might be amenable to manipulation by drugs or vaccines.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Receptores de Citocinas
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Células TH1
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Malaria
Idioma:
En
Revista:
J Immunol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Reino Unido