Inhibition of caspase-8 activity promotes protective Th1- and Th2-mediated immunity to Leishmania major infection.
J Leukoc Biol
; 95(2): 347-55, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24072877
ABSTRACT
We investigated how apoptosis pathways mediated by death receptors and caspase-8 affect cytokine responses and immunity to Leishmania major parasites. Splenic CD4 T cells undergo activation-induced apoptosis, and blockade of FasL-Fas interaction increased IFN-γ and IL-4 cytokine responses to L. major antigens. To block death receptor-induced death, we used mice expressing a T cell-restricted transgene for vFLIP. Inhibition of caspase-8 activation in vFLIP mice enhanced Th1 and Th2 cytokine responses to L. major infection, even in the Th1-prone B6 background. We also observed increased NO production by splenocytes from vFLIP mice upon T cell activation. Despite an exacerbated Th2 response, vFLIP mice controlled better L. major infection, with reduced lesions and lower parasite loads compared with WT mice. Moreover, injection of anti-IL-4 mAb in infected vFLIP mice disrupted control of parasite infection. Therefore, blockade of caspase-8 activity in T cells improves immunity to L. major infection by promoting increased Th1 and Th2 responses.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leishmaniose
/
Leishmania major
/
Células Th2
/
Células Th1
/
Caspase 8
/
Imunidade Celular
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Brasil