Disease Susceptibility and Cytokine Production in Sab Mice Following Infection with Leishmania Donovani

Abstract

Murine models have been used for studies on human leishmaniasis. Mice susceptibility to Leishmania donovani differs significantly between the Swiss albino and BALB/c strains. Whereas BALB/c is highly susceptible, Swiss Albino shows resistance to L. donovani infection. While it has been possible to study visceral leishmaniasis using both highly susceptible and resistant animal models, clinical features including disease course and immunological outcomes between the extremes have not been extensively studied probably due to lack of a suitable model. The present study uses the SAB mice, obtained by crossing the BALB/c mice with the Swiss Albino mice. The objective of the present study was to investigate and compare the susceptibility of the SAB mice, the Swiss albino and BALB/c mice (SAB) to L. donovani infection. In addition, study compared serum interferon gamma (INF-γ) and interleukin-4 (IL-4) levels between the SAB mice, Swiss albino and BALB/c mice. Fifteen mice of each of the SAB, Swiss albino and BALB/c mice were infected intraperitoneally with 2 x 106 virulent L. donovani parasites investigated for a total of 8 weeks. Another set of 10 mice of each of the SAB, Swiss albino and BALB/c mice strains were used as uninfected controls. Body weights were measured during and at the end of the experimental period. Following 8 weeks of L. donovani infection, the spllen weights were taken from experimental and control mice. Serum samples were prepared and used for quantification of INF-γ and IL-4 cytokines. The spleen and liver tissues were prepared and stained with hematoxylin-eosin stain and observed for histopathological changes. Data were analysed using STATA software and utilized single parameter analysis of variance (ANOVA) followed by Tukey test were applicable. Photography was done for histopathological results. A P of < 0.05 was indicated to be of statistical significance. Findings indicated that the body and splenic weights of SAB mice were intermediate between those of Swiss albino and BALB/c mice; however, there was no significant difference (P>0.05) between these results. The L. donovani infected SAB had intermediate levels of IL-4 while the Swiss albino had the highest levels with BALB/c having the least amounts of the cytokine. These IL-4 levels were higher than those recorded in the corresponding control mice groups. The L. donovani infected Swiss albino mice produced significantly higher IFN-γ levels compared to the SAB (P=0.0216) or BALB/c (P=0.0326) mice. The IFN-γ levels in the SAB mice were intermediate between the Swiss albino and BALB/c mice. Pathologically, there was observable liver proliferation of kupffer cells, degenerated hepatocytes and fibrosis in BALB/c and SAB mice. In addition, there was chronic degeneration of structure of their spleen indicating severe infection. Spleen and liver tissues of the Swiss albino mice were normal or near normal. On the basis of the present report, this study concludes that, the SAB mice infected with L. donovani parasites presents with disease features and immunological parameters intermediate between the BALB/c mice which is susceptible and Swiss albino mice which is resistant to disease. It is therefore, recommended that the SAB mice can be used for visceral leishmaniasis studies aimed at understanding disease course and immunological outcome intermediate between severe and subclinical disease.