Murine experimental leprosy: Evaluation of immune response by analysis of peritoneal lavage cells and footpad histopathology

Abstract

Summary This study evaluated the immune response of nude and BALB/c mice inoculated in the footpads (FP) with Mycobacterium leprae after 3, 5 and 8 months. At each timepoint peritoneal cells, peripheral blood, FP and popliteal lymph nodes (PLN) were collected. Peritoneal cell cultures were performed to measure the H2O2, O2−, NO, IL‐2, IL‐4, IL‐10, IL‐12, IFN‐γ and TNF levels. Serum levels of anti‐PGL‐I antibodies were also quantified. The results showed that the infection was progressive in nude mice with bacterial multiplication, development of macroscopic lesions in the FP and presence of bacilli in the PLN at 8 months. In BALB/c mice, the infection reached a plateau of bacillary multiplication at 5 months and regressed at 8 months. Histopathological analysis of FP revealed a mononuclear inflammatory infiltrate with a large number of neutrophils at 5 months, with a higher number in nude mice. At 8 months, the number of neutrophils decreased and the infiltrate was predominantly mononuclear in both mouse strains. There was no H2O2, O2−, IL‐2, IL‐4, IL‐10 and IFN‐γ production in the course of infection in nude mice; however, in BALB/c, O2− and IL‐12 production was higher at 5 months and NO, IFN‐γ and TNF production was higher at 8 months when there was a decrease in the number of bacilli. The level of anti‐PGL‐I antibodies was higher in BALB/c mice. Thus, nude and BALB/c mice can be used as experimental models for the study of various aspects of leprosy.

Avaliação do perfil de citocinas séricas e óxido nítrico na hanseníase experimental murina

“…Nos camundongos BALB/c, a dosagem sérica de TNF e IFN-γ revelou níveis maiores aos 8 meses, porém sem diferença estatisticamente significante, sugerindo um possível perfil Th1 como observado em pacientes TT. O aumento dos níveis dessas citocinas também foi observado em sobrenadante de cultura de células peritoneais de camundongos BALB/c inoculados com M. leprae após 8 meses, corroborando com os nossos achados 14 .…”

“…Quanto à resposta imune em modelos experimentais, camundongos BALB/c e atímicos, quando inoculados com M. leprae no coxim plantar, apresentam comportamentos distintos, isto é, enquanto nos BALB/c os bacilos permanecem apenas no coxim plantar com lesões granulomatosas semelhantes as lesões de pacientes TT 14 , nos camundongos nude existe intensa multiplicação bacilar com disseminação dos bacilos para outras áreas, além do coxim plantar, apresentando lesões predominantemente macrofágicas com numerosos bacilos no seu interior semelhantes aquelas de pacientes LL 14 .…”