Emergence of an effective adaptive cell mediated immune response to Mycobacterium leprae is not impaired in reactive oxygen intermediate-deficient mice.
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.
Hagge
Deanna A
DA
Immunology Research Department, National Hansen's Disease Programs, Laboratory Research Branch, Baton Rouge, LA 70803, USA.
Marks
Vilma T
VT
Ray
Nashone A
NA
Dietrich
Marilyn A
MA
Kearney
Michael T
MT
Scollard
David M
DM
Krahenbuhl
James L
JL
Adams
Linda B
LB
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D007111:Immunity, Cellular; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009166:Mycobacterium leprae / Q000276:immunology*; D019255:NADPH Oxidases / Q000502:physiology*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D016207:Cytokines; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases