| First Author | Pereira-Manfro WF | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 95 |
| Issue | 2 | Pages | 347-55 |
| PubMed ID | 24072877 | Mgi Jnum | J:318217 |
| Mgi Id | MGI:6858802 | Doi | 10.1189/jlb.0912463 |
| Citation | Pereira-Manfro WF, et al. (2014) Inhibition of caspase-8 activity promotes protective Th1- and Th2-mediated immunity to Leishmania major infection. J Leukoc Biol 95(2):347-55 |
| abstractText | 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-gamma 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. |
