Leishmania (Leishmania) chagasi-infected mice as a model for the study of glomerular lesions in visceral leishmaniasis

Abstract

Renal involvement in visceral leishmaniasis (VL) is very frequent but the pathogenesis of this nephropathy is poorly understood. In previous studies using dogs with VL we have detected new immunopathological elements in the glomeruli such as T cells and adhesion molecules. Although Leishmania (Leishmania) chagasi-infected dogs and hamsters are considered to be good models for VL, their use is limited for immunopathologic studies. The use of isogenic mouse strains susceptible to L. (L.) chagasi infection was an alternative but, on the other hand, the renal lesions of these animals have not yet been characterized. Thus, our purpose in the present study was to characterize mice infected with L. (L.) chagasi as a suitable model to study VL nephropathy. Kidney samples were obtained from control mice (N = 12) and from BALB/c mice (N = 24) injected intraperitoneally with 20 million L. (L.) chagasi amastigotes 7, 15, and 30 days after injection and processed for histopathological studies and detection of IgG deposits. Glomerular hypercellularity was clearly visible and, upon Mason's trichrome and periodic acid methenamine silver staining, a pattern suggestive of mesangial proliferative glomerulonephritis was observed in mice with VL. Time-dependent IgG deposits were also seen in infected mice. We consider L. (L.) chagasi-infected mice to be a suitable model for studies of the immunopathogenesis of glomerular lesions in VL.

Renal Histopathological Findings in Dogs With Visceral Leishmaniasis

“…A study by BENDERITTER et al 3 found 72.7% with glomerular lesions characterized by acute and membranous glomerulonepthritis. Studies using mice 21 and hamster 22 models observed mesangial proliferative glomurolonephritis.…”

“…In the present study the histological pattern was found equal to membranous (18%) and membranoproliferative glomerulonephritis (18%), followed by segmental and focal glomerulosclerosis (14%). An experimental model showed histological alterations from 7-14 days post infection 21 . Since the animals in this study were naturally infected, there was no control over the time of infection, which may influence the degree of the alterations described here.…”

Renal involvement in leishmaniasis: a review of the literature

“…Immune complex deposition, T cells and adhesion molecules activation have been shown to be important mechanisms of injury in the glomerulonephritis occurring in visceral leishmaniasis [ 11 – 15 ]. In 2007, Prianti et al [ 16 ] observed a mesangial proliferative pattern of glomerulonephritis in Leishmania chagasi -infected mice. The presence of IgG deposits and the absence of C3b deposits in the glomeruli suggested that immunoglobulins may be involved in the pathogenesis of glomerular injury caused by kala-azar, while the complement did not seem to play an important role in the disease.…”

Leishmanicidal Activity of Piper nigrum Bioactive Fractions is Interceded via Apoptosis In Vitro and Substantiated by Th1 Immunostimulatory Potential In Vivo

“…In vitro toxicity of P. nigrum bioactive fractions had earlier been studied against RAW macrophages where it was observed that both PNH and PNE possessed high CC 50 (50% inhibitory concentration against macrophages) of 379.7 and 200 μg ml -1 , respectively, and were specific against L. donovani amastigotes ( Chouhan et al, 2014b ). Hepatomegaly is one of the characteristic clinical symptoms of VL and during the establishment of infection, renal functions are also severely impaired ( Prianti et al, 2007 ). There was a significant increase in enzymatic activity of SGOT, SGPT, and ALP as well as urea and creatinine concentration in INF and VC groups.…”