02333nas a2200337   4500000000100000008004100001260001300042653001200055653001400067653002300081653001600104653000900120653002300129653002500152653001900177653003000196653002800226100001200254700001200266700001100278700001500289700001400304700001500318700001800333700001300351245015700364300001100521490000700532520144200539022001401981       2007                            d  c2007 Oct10aAnimals10aCytokines10aImmunity, Cellular10aMacrophages10aMice10aMice, Inbred C57BL10aMycobacterium leprae10aNADPH Oxidases10aReactive Nitrogen Species10aReactive Oxygen Species1 aHagge D1 aMarks V1 aRay NA1 aDietrich M1 aKearney M1 aScollard D1 aKrahenbuhl JL1 aAdams LW00aEmergence of an effective adaptive cell mediated immune response to Mycobacterium leprae is not impaired in reactive oxygen intermediate-deficient mice.  a92-1010 v513 a<p>Cytokine-activated macrophages (MPhi) 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 (phox91-/-) was examined. Mycobacterium leprae multiplication in phox91-/- 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 MPhi from B6 and phox91-/- mice supported bacterial viability, whereas IFNgamma-activated MPhi killed M. leprae in a RNI-dependent manner, emphasizing that ROI was dispensable. These data show that phox91-/- mice generate a strong adaptive immune response and control long-term infection with M. leprae.</p>  a0928-8244