Interferon Gamma Unresponsiveness Due to Down-Regulation of IFN-γR Expression in Experimental Cutaneous Leishmaniasis

It is now well documented that interferon gamma (IFN-γ) is the indispensable cytokine for inducing protective immunity against experimental and human cutaneous leishmaniaisis. The importance of IFN-γ receptor (IFN-γR) 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-γR in vivo. In addition, we studied the responsiveness to IFN-γ ex vivo. To do that, we assessed the expression of CD119 (IFN-γRα ) 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-γ in order to study the function of IFN-γR. NO production by draining lymph nodes cells of infected C57BL/6 mice in response to recombinant murine IFN-γ was significantly higher than the cells of infected BALB/c mice (37.5 ± 0.6 and 11.6 ± 0.5 µM respectively, p<0.05). Therefore, our results confirm the in vitro reports regarding the impairment of IFN-γ responsiveness due to Leishmania infection.