Disease Susceptibility and Cytokine Production in Sab Mice Following Infection with Leishmania Donovani
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Date
2021
Authors
Ngetich, Rose Chemutai
Journal Title
Journal ISSN
Volume Title
Publisher
Kenyatta University
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.
Description
A Thesis Submitted in Partial Fulfillment of the Requirements for the Award of the Degree of Master of Science (Applied Parasitology) in the School of Pure and Applied Sciences of Kenyatta University, November, 2021
Keywords
Disease Susceptibility, Cytokine Production, Sab Mice, Following Infection, Leishmania Donovani