Induction and treatment of anergy in murine leprosy

Abstract

Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the genetic and immunological characteristics of the patient and on the characteristics of the leprosy bacillus. The malignant manifestations of lepromatous leprosy result from the mycobacterial-specific anergy that develops in this form of the disease. Using murine leprosy as a model of anergy in this study, we first induced the development of anergy to Mycobacterium lepraemurium (MLM) in mice and then attempted to reverse it by the administration of dialysable leucocyte extracts (DLE) prepared from healthy (HLT), BCG-inoculated and MLM-inoculated mice. Mice inoculated with either MLM or BCG developed a robust cell-mediated immune response (CMI) that was temporary in the MLM-inoculated group and long-lasting in the BCG-inoculated group. DLE were prepared from the spleens of MLM- and BCG-inoculated mice at the peak of CMI. Independent MLM intradermally-inoculated groups were treated every other day with HLT-DLE, BCG-DLE or MLM-DLE, and the effect was documented for 98 days. DLE administered at a dose of 1.0 U (1 × 10(6) splenocytes) did not affect the evolution of leprosy, while DLE given at a dose of 0.1 U showed beneficial effects regardless of the DLE source. The dose but not the specificity of DLE was the determining factor for reversing anergy.

Chronic infection with Mycobacterium lepraemurium induces alterations in the hippocampus associated with memory loss

“…2 . Quantitation of bacilli was achieved using IMAGE J software and the units were given in pixels 12 . Measurements were performed on 4-μm paraffin sections stained for acid-fast bacilli (Ziehl-Neelsen).…”

“…The progressive decrease in cell-mediated immunity, CMI (anergy), is characteristic of chronic infectious diseases produced by pathogenic mycobacteria 12 , 29 , 30 . Here, we showed that infection of mice with Mycobacterium lepraemurium ( MLM ) led to a disseminated, multiorgan, infection that did not directly affect CNS 15 .…”

“…Images were taken in a Nikon Eclipse E8000 microscope (Tokyo, Japan). Bacillary density in the liver and spleen was quantified using Image J software and the results were given as red pixels 12 .…”

“…anergy, hypercholesterolemia, and neurodegeneration, respectively) 9 – 11 . These long-term systemic alterations have been described in natural and experimental models of infection 12 , 13 .…”

Evaluación inmunológica durante el tratamiento de un caso de lepra dimorfa lepromatosa

“…En un modelo experimental murino de lepra, la mejoría clínica de los animales infectados y tratados con EDL se evidenció con la reducción en la extensión y número de bacilos en los granulomas, así como en el desarrollo de tejido de granulación, indicativo de mejoría clínica, la cual fue mayor en los ratones que recibieron EDL combinado con bactericidas. 10,11 En el paciente descrito, al igual que en el modelo murino, se redujo el tamaño de los nódulos y la sintomatología clínica. Además, se registraron cambios en la citometría que sugieren reforzamiento del perfil Th1: se incrementaron los linfocitos CD4 y las células NK y se redujeron levemente las CD19.…”