The resolution of lesions induced by Leishmania major in mice requires a functional Fas (APO-1, CD 95) pathway of cytotoxicity
✍ Scribed by Fatima Conceição-Silva; Michael Hahne; Michael Schröter; Jacques Louis; Jürg Tschopp
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 153 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Normal or perforin-deficient C57BL/6 mice are able to heal spontaneously cutaneous lesions induced by Leishmania major. In this report, we show that syngeneic gld and lpr mice, lacking a functional Fas system, fail to heal their lesions. This inability to control infection could not be attributed either to a failure to mount a protective CD4+ Th1 response or to an unresponsiveness of their macrophages to the activating signals of IFN-gamma. The observation showing that administration of exogenous recombinant Fas ligand (FasL) to FasL-deficient mice resulted in the resolution of cutaneous lesions demonstrates the importance of the Fas-FasL pathway in the elimination of parasites. Furthermore, macrophages infected with L. major in vitro up-regulate their surface expression of Fas in response to IFN-gamma and as a result become susceptible to CD4+ T cell-induced apoptotic death. These results suggest that the CD4+ T cell-induced apoptotic death of MHC class II-expressing antigen-presenting cells, observed in vitro and operating through the Fas (Apo-1/CD95) pathway, is relevant in vivo.