Interferon Gamma unresponsiveness Due to Down - Regulation of IFN - yR Expression in Experimental Cutaneous Leishmaniasis

It is now well documented that interferon gamma (IFN-g) is the indispensable cytokine for inducing protective immunity against experimental and human cutaneous leishmaniaisis. The importance of IFN-g receptor (IFN-gR) has also been studied. In the present study, we made attempts to find out whether L. major infection is able to alter the expression of IFN-gR in vivo. In addition, we studied the responsiveness to IFN-g ex vivo. To do that, we assessed the expression of CD119 (IFN-gRa) on CD45+ cells isolated from draining lymph nodes of infected and uninfected BALB/c and C57BL/6 mice by flow cytometry. The MFI (mean fluorescence intensities) of CD119 on uninfected BALB/c mice were 192.8 ± 18.4 but the CD119 MFI of infected BALB/c mice were remarkably decreased (107.9±40.8). CD119 MFI of uninfected and infected C57BL/6 mice were 276.2 ± 17.1 and 140.4±43.0 respectively Moreover, we measured the production of nitric oxide (NO) by these cells in the presence of IFN-g in order to study the function of IFN-gR. NO production by draining lymph nodes cells of infected C57BL/6 mice in response to recombinant murine IFN-g was significantly higher than the cells of infected BALB/c mice (37.5 ± 0.6 and 11.6 ± 0.5 mM respectively, p<0.05). Therefore, our results confirm the in vitro reports regarding the impairment of IFN-g responsiveness due to Leishmania infection. Iran. Biomed.