Study of murine experimental Jorge Lobo's disease by analysis of peritoneal lavage cells and footpad histopathology: early versus chronic lesions

Abstract

The murine model of Jorge Lobo's disease is characterized by histological alterations similar to those seen in human disease, including a large number of viable fungi. This study evaluated the immune response of mice with early and late macroscopic lesions (5 and 13 months post-inoculation [p.i.], respectively) by the analysis of peritoneal lavage cells and footpad (FP) histology. The FP of mice were inoculated with 1 × 10(6) fungi (viability index of 41%). At 5 and 13 months p.i., the granuloma mainly consisted of macrophages and multinucleated giant cells, but a larger number of neutrophils was observed at 5 months and lymphocytes at 13 months. The number of fungi in the FP and fungal viability were 1.8 ± 1.1 × 10(6) fungi/ml and 38.5% at 5 months p.i. and 30.8 ± 11.7 × 10(6) fungi/ml and 9% at 13 months (P < .05). Higher production of H₂O₂, O₂(-), IL-10, and TNF-α were observed at 13 months (P < .05), but there was no significant difference in the production of NO, IL-2, IL-4, IL-12 and IFN-γ. The results showed significant differences between early and late lesions and support the use of BALB/c mice for evaluation of the different phases of infection.

Nutritional status and immune response in murine experimental Jorge Lobo's disease

“…With respect to cytokine production, the present study revealed lower levels of IL-12 and IFN-c in the malnourished groups (G1 and G2) compared to healthy animals (G4) and no difference in IL-4 levels. These results agree with those reported for malnourished mice inoculated or not 30 with L. donovani, 31 L. chagasi 7 and M. tuberculosis 9 and suggest a smaller participation of Th1 cytokines in the interaction between malnutrition and infection.…”

“…However, a recent study showed higher production of H 2 O 2 and O 2 À by peritoneal macrophages at 13 months when compared with 5 months postinoculation in murine experimental Jorge Lobo's disease, suggesting that reactive oxygen intermediates seem to play an important role in the lyses of the fungus. 29 The results of quantification of NO in malnourished animals are similar to those reported by Anstead et al [30] for not inoculated malnourished animals, who observed a reduction in NO production when compared to healthy animals. When studying malnourished animals inoculated with Leishmania donovani, these authors also found lower NO production in these animals compared to the healthy group.…”

“… the presence of constitutive melanin in the cell wall of the fungus may confer resistance to the reactive oxygen intermediates produced by macrophages. However, a recent study showed higher production of H 2 O 2 and O 2 − by peritoneal macrophages at 13 months when compared with 5 months postinoculation in murine experimental Jorge Lobo's disease, suggesting that reactive oxygen intermediates seem to play an important role in the lyses of the fungus …”