Emergence of an effective adaptive cell mediated immune response toMycobacterium lepraeis not impaired in reactive oxygen intermediate-deficient mice

Abstract

Cytokine-activated macrophages (MF) 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 CD62Lhi 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 MF from B6 and phox91 À/À mice supported bacterial viability, whereas IFNg-activated MF killed M. leprae in a RNI-dependent manner, emphasizing that ROI was dispensable. These data show that phox91 À/À mice generate a strong adaptive immune response and control long-term infection with M. leprae.

Insights from animal models on the immunogenetics of leprosy: a review

“…Since lymph node cells are typically easy to obtain and of sufficient number for advanced methods of analyses, they have been studied in place of the granuloma population and regarded as representative of the immuneprotective response. In our studies, however, we found a striking difference in the cellular composition at the site of infection itself and the popliteal lymph nodes draining this site (Hagge et al 2007(Hagge et al , 2009. While the lymph nodes of M. leprae-infected immunocompetent mice are composed of B cells and naïve CD4 + T cells, the lymphocytes which infiltrate the foot pads are primarily CD4 + effector T cells, presumably there due to a selective immigration or retention of these cells in the granuloma (Table I).…”

“…In our gene knockout mouse studies, we have utilized the Shepard model and a higher dose lepromin test-like model (Adams et al 2000, Cooper et al 2002a, Hagge et al 2007). The Shepard model is used for bacterial growth and enumeration and molecular and histological evaluation.…”

Lymphotoxin-α and TNF Have Essential but Independent Roles in the Evolution of the Granulomatous Response in Experimental Leprosy

“…High dose infection model: Each hind FP was inoculated with 3 ϫ 10 7 M. leprae in 0.03 ml PBS, 25 and induration was measured weekly using a Vernier caliper. At 3 months post-infection, FP tissues were harvested for histopathological and immunohistochemical analyses, …”

“…26,27 Sections were viewed and captured on a Zeiss Axioplan microscope (Zeiss, Germany) equipped with a MicroFire camera and PictureFrame software. 25 …”

“…Data were normalized for template variation by dividing each gene transcript value by that of the glyceraldehyde-3-phosphate dehydrogenase RNA RT-PCR value for the same template. 25 …”