Emergence of an effective adaptive cell mediated immune response to Mycobacterium leprae is not impaired in reactive oxygen intermediate‐deficient mice

Cytokine‐activated macrophages (MΦ) employ reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) to combat pathogens. The requirement for ROI for an effective host response to experimental leprosy using mice which have a disruption in the 91‐kD subunit of the NAPDH oxidase cytochrome b ( phox 91 −/− ) was examined. Mycobacterium leprae multiplication in phox 91 −/− foot pads (FP) was elevated early in infection but subsequently arrested similarly to control mice within a noninvasive granuloma. Using a modified lepromin test model, a similar cellular composition in the M. leprae ‐induced FP granuloma in both strains with lymphocyte infiltration consisting primarily of CD4 + CD44 hi CD62L lo effector cells was found. Of great interest was the disparity in the T cell population between the granuloma and the draining lymph node which contained predominantly naïve CD4 + CD44 lo CD62L hi cells and was, therefore, not representative of the infection site. TH1 cytokines, chemokines and inducible nitric oxide synthase were comparably expressed in the FP of both strains. When infected in vitro , normal MΦ from B6 and phox 91 −/− mice supported bacterial viability, whereas IFNγ‐activated MΦ killed M. leprae in a RNI‐dependent manner, emphasizing that ROI was dispensable. These data show that phox 91 −/− mice generate a strong adaptive immune response and control long‐term infection with M. leprae .