Disease progression and immune responses in f1 cross-breed between balb/c and swiss albino mice infected with leishmania major
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Date
2014-08-28
Authors
Kiige, Samuel Githuku
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Abstract
Human infections with leishmaniasis have been historically investigated using murine models such as BALB/c mice. Questions are arising over the high susceptibility of BALB/c mice to Leishmania major and not L. donovani and other Leishmania species. This was systematically recognized and Swiss mice adopted as a model. Swiss mice are highly resistance to Leishmania infections in concordance with observed response in humans. Developing a model that shows characteristics of both strains was proposed involving a cross-breed between BALB/c and Swiss mice. As yet, response of the cross-breed to Leishmania infection is superficial. The aim of the present study is to determine the disease progression, cytokines production and antibody response in L. major infected F1 cross-breed between BALB/c and Swiss albino mice. The resistant Swiss mice was crossbred with a susceptible BALB/c mice. The resultant F1 generation mice were infected intradermaly (ID) with stationary phase L. major parasites (strain IDUB/KE/94=NLB-144) with parental strains as controls. Disease progression was studied from the baseline by measuring lesion sizes on the infected footpad weekly and compared to the same footpad before infection. The parasite metastasis to visceral organs was established by determining Leishman-Donovan Units (LDU) in the spleen. Chemokines (MCP-1 and MIP-1α) and cytokine interferon-gamma (IFN-) profiles as well as anti-Leishmanial IgG antibody production, were determined in blood serum based on Enzyme-linked Immunosorbent Assay (ELISA). The study found that BALB/c mice had the largest lesion size while Swiss mice had the smallest lesion size. The F1 mice had lesion sizes which were intermediate between those of BALB/c and Swiss mice. The spleen weight of the F1 mice was lowest without any discernible differences between that of BALB/c and Swiss mice. In terms of spleno-somatic index, BALB/c had the highest followed by the F1 mice while Swiss had the lowest. BALB/c had the highest LDU among the groups followed by Swiss mice while F1 generation mice indicating the lowest. BALB/c had the highest footpad amastigotes followed by the F1 mice while Swiss had the lowest counts. The cytokine (IFN- levels) production was highest in Swiss followed by F1 mice while in BALB/c mice were the lowest. The chemokine (MIP-1α and MCP-1) production among the groups after eight weeks of experiment was highest in Swiss, while BALB/c mice had the lowest levels, F1 mice had intermediate levels. The highest production of anti-Leishmanial IgG antibody was observed in BALB/c mice while the lowest levels were observed in the F1 mice with Swiss mice producing intermediate levels of the antibody. Considering the lesion sizes due to L. major infection, the ability to clear the parasites in the body and the immune responses, the F1 generation mice should be considered as a suitable experimental model for studies of other Leishmania species. However, its susceptibility to the disease and observed immunological reactions should be investigated further to ascertain the role of genetics in influencing the disease course.
Description
Master of Science (Immunology). 93p. May, 2014. RC 153 .K5