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Evaluation of parasitological and immunological parameters of Leishmania chagasi infection in BALB/c mice using different doses and routes of inoculation of parasites

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Abstract

Experimental vaccines to protect against visceral leishmaniasis (VL) have been developed by using BALB/c mice infected with a large (107 to 108) inoculum of parasites. Remarkably, prior literature has reported that the poor protection observed is mainly due to the high susceptibility of this strain. To determine factors inherent to mice that might abrogate vaccine-induced efficacy, the present research sought to investigate the impact of the administration of different infective inoculums of Leishmania chagasi (syn. L. infantum) in BALB/c mice, evaluating subcutaneous and intravenous routes of administration as well as parasitological and immunological parameters over different periods of time. This study shows that the injection of a highly infective inoculum in mice, through both subcutaneous and intravenous routes, results in a sustained infection. The mice developed a high parasite load in the liver; however, these values diminished over time. This result did not corroborate with the parasite load in the bone marrow and brain and proved to be expressively different in the spleen and draining lymph nodes, where the values increased over time. Mice infected with a low dose of parasites (103) showed a certain resistance against infection, based mainly on the IFN-γ and oxide nitric production. Considering all the elements, it could be concluded that the models employing high doses (107) of L. chagasi in BALB/c mice can bring about an imbalance in the animals’ immune response, thus allowing for the development of the disease at the expense of efficacy within the vaccine candidates.

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Acknowledgments

This study was supported by grants from Pró-Reitoria de Pesquisa from UFMG (Edital 08/2011), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG; CBB-APQ-01322-08), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; APQ-577483/2008-0), and Instituto Nacional de Ciência e Tecnologia em Nanobiofarmacêutica (INCT/Nano-BIOFAR), CNPq. DGV and EAFC are grant recipients of CNPq, while DMO, MAFC, and MACF are grant recipients of Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil

    Dulcilene M. Oliveira

  2. Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil

    Mariana Amália F. Costa, Diogo G. Valadares, Vivian T. Martins & Carlos Alberto P. Tavares

  3. Programa de Pós-Graduação em Medicina Molecular, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil

    Miguel A. Chavez-Fumagalli

  4. Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil

    Mariana C. Duarte, Lourena E. Costa & Eduardo Antonio F. Coelho

  5. Departamento de Parasitologia, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil

    Rosângela F. Gomes & Maria N. Melo

  6. Centro de Biología Molecular Severo Ochoa, CSIC, UAM, Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049, Madrid, Spain

    Manuel Soto

  7. Laboratório de Biotecnologia Aplicada ao Estudo das Leishmanioses, Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Campus Pampulha, Avenida Antônio Carlos, 6627, 31.270-901, Belo Horizonte, Minas Gerais, Brazil

    Eduardo Antonio F. Coelho

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  1. Dulcilene M. Oliveira
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  2. Mariana Amália F. Costa
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  3. Miguel A. Chavez-Fumagalli
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  4. Diogo G. Valadares
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  5. Mariana C. Duarte
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  6. Lourena E. Costa
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  7. Vivian T. Martins
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  8. Rosângela F. Gomes
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  9. Maria N. Melo
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  10. Manuel Soto
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  11. Carlos Alberto P. Tavares
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  12. Eduardo Antonio F. Coelho
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Correspondence to Eduardo Antonio F. Coelho.

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Oliveira, D.M., Costa, M.A.F., Chavez-Fumagalli, M.A. et al. Evaluation of parasitological and immunological parameters of Leishmania chagasi infection in BALB/c mice using different doses and routes of inoculation of parasites. Parasitol Res 110, 1277–1285 (2012). https://doi.org/10.1007/s00436-011-2628-5

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