Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-22T05:27:59.190Z Has data issue: false hasContentIssue false
  • English
  • Français

Distinct courses of infection with Leishmania (L.) amazonensis are observed in BALB/c, BALB/c nude and C57BL/6 mice

Published online by Cambridge University Press:  19 February 2016

LEONARDO G. VELASQUEZ ,
MARIANA K. GALUPPO ,
ELOIZA DE REZENDE ,
WESLEY N. BRANDÃO ,
JEAN PIERRE PERON ,
SILVIA R. B. ULIANA ,
MARIA IRMA DUARTE  and
BEATRIZ S. STOLF
LEONARDO G. VELASQUEZ
Affiliation:
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
MARIANA K. GALUPPO
Affiliation:
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
ELOIZA DE REZENDE
Affiliation:
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
WESLEY N. BRANDÃO
Affiliation:
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
JEAN PIERRE PERON
Affiliation:
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
SILVIA R. B. ULIANA
Affiliation:
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
MARIA IRMA DUARTE
Affiliation:
Department of Pathology, University of São Paulo School of Medicine, São Paulo, Brazil
BEATRIZ S. STOLF*
Affiliation:
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
*
*Corresponding author: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. E-mail: bstolf@usp.br
Get access Rights & Permissions [Opens in a new window]

Summary

Leishmania (L.) amazonensis [L. (L.) amazonensis] is widely distributed in Brazil and its symptomatic infections usually lead to few localized lesions and sometimes to diffuse cutaneous form, with nodules throughout the body, anergy to parasite antigens and poor therapeutic response. The variability of these manifestations draws attention to the need for studies on the pathophysiology of infection by this species. In this study, we analysed the course and immunological aspects of L. (L.) amazonensis infection in BALB/c and C57BL/6 strains, both susceptible, but displaying different clinical courses, and athymic BALB/c nude, to illustrate the role of T cell dependent responses. We analysed footpad thickness and parasite burden by in vivo imaging. Furthermore, we evaluated the cellular profile and cytokine production in lymph nodes and the inflammatory infiltrates of lesions. Nude mice showed delayed lesion development and less inflammatory cells in lesions, but higher parasite burden than BALB/c and C57BL/6. BALB/c and C57BL/6 mice had similar parasite burdens, lesion sizes and infiltrates until 6 weeks after infection, and after that C57BL/6 mice controlled the infection. Small differences in parasite numbers were observed in C57BL/6 macrophages in vitro, indicating that in vivo milieu accounts for most differences in infection. We believe our results shed light on the role of host immune system in the course of L. (L.) amazonensis infection by comparing three mouse strains that differ in parasitaemia and inflammatory cells.

Keywords

Leishmania (L.) amazonensisinfection courseparasite burdenin vivo imagingmouse strainsnude miceimmune responseinflammation
Type
Research Article
Information
Parasitology , Volume 143 , Issue 6 , May 2016 , pp. 692 - 703
Check for updates
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Abreu-Silva, A. L., Calabrese, K. S., Cupolilo, S. M., Cardoso, F. O., Souza, C. S. and Goncalves da Costa, S. C. (2004). Histopathological studies of visceralized Leishmania (Leishmania) amazonensis in mice experimentally infected. Veterinary Parasitology 121, 179–187.Google Scholar
Afonso, L. C. and Scott, P. (1993). Immune responses associated with susceptibility of C57BL/10 mice to Leishmania amazonensis . Infection Immunity 61, 2952–2959.Google Scholar
Alvar, J., Velez, I. D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J. and den Boer, M. (2012). Leishmaniasis worldwide and global estimates of its incidence. PLoS ONE 7, e35671.Google Scholar
Balestieri, F. M., Queiroz, A. R., Scavone, C., Costa, V. M., Barral-Netto, M. and Abrahamsohn Ide, A. (2002). Leishmania (L.) amazonensis-induced inhibition of nitric oxide synthesis in host macrophages. Microbes and Infection 4, 23–29.CrossRefGoogle ScholarPubMed
Beattie, L., Evans, K. J., Kaye, P. M. and Smith, D. F. (2008). Transgenic Leishmania and the immune response to infection. Parasite Immunology 30, 255–266.CrossRefGoogle ScholarPubMed
BRASIL (2010). Manual de Vigilância da Leishmaniose Tegumentar Americana. Ministério da Saúde, Secretaria de Vigilância em Saúde, 2nd Edn. Editora do Ministerio da Saude, Brasilia.Google Scholar
Buxbaum, L. U. (2015). Interleukin-10 from T cells, but not macrophages and granulocytes, is required for chronic disease in Leishmania mexicana infection. Infection and Immunity 83, 1366–1371.CrossRefGoogle Scholar
Cupolilo, S. M., Souza, C. S., Abreu-Silva, A. L., Calabrese, K. S. and Goncalves da Costa, S. C. (2003). Biological behavior of Leishmania (L.) amazonensis isolated from a human diffuse cutaneous leishmaniasis in inbred strains of mice. Histology and Histopathology 18, 1059–1065.Google ScholarPubMed
de Oliveira Cardoso, F., de Souza Cda, S., Mendes, V. G., Abreu-Silva, A. L., Goncalves da Costa, S. C. and Calabrese, K. S. (2010). Immunopathological studies of Leishmania amazonensis infection in resistant and in susceptible mice. Journal of Infectious Diseases 201, 1933–1940.Google Scholar
Felizardo, T. C., Toma, L. S., Borges, N. B., Lima, G. M. and Abrahamsohn, I. A. (2007). Leishmania (Leishmania) amazonensis infection and dissemination in mice inoculated with stationary-phase or with purified metacyclic promastigotes. Parasitology 134, 1699–1707.Google Scholar
Felizardo, T. C., Gaspar-Elsas, M. I., Lima, G. M. and Abrahamsohn, I. A. (2012). Lack of signaling by IL-4 or by IL-4/IL-13 has more attenuating effects on Leishmania amazonensis dorsal skin – than on footpad-infected mice. Experimental Parasitology 130, 48–57.Google Scholar
Flanagan, S. P. (1966). ‘Nude’, a new hairless gene with pleiotropic effects in the mouse. Genetical Research 8, 295–309.Google Scholar
Gontijo, B. and de CarvalhoMde, L. (2003). American cutaneous leishmaniasis. Revista da Sociedade Brasileira de Medicina Tropical 36, 71–80.Google Scholar
Heinzel, F. P., Sadick, M. D., Holaday, B. J., Coffman, R. L. and Locksley, R. M. (1989). Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. Journal of Experimental Medicine 169, 59–72.Google Scholar
Henderson, R. B., Hobbs, J. A., Mathies, M. and Hogg, N. (2003). Rapid recruitment of inflammatory monocytes is independent of neutrophil migration. Blood 102, 328–335.CrossRefGoogle ScholarPubMed
Hsu, A. C. and Scott, P. (2007). Leishmania mexicana infection induces impaired lymph node expansion and Th1 cell differentiation despite normal T cell proliferation. Journal of Immunology 179, 8200–8207.Google Scholar
Ji, J., Masterson, J., Sun, J. and Soong, L. (2005). CD4+CD25+ regulatory T cells restrain pathogenic responses during Leishmania amazonensis infection. The Journal of Immunology 174, 7147–7153.CrossRefGoogle ScholarPubMed
Ji, J., Sun, J., Qi, H. and Soong, L. (2002). Analysis of T helper cell responses during infection with Leishmania amazonensis . American Journal of Tropical Medicine and Hygiene 66, 338–345.CrossRefGoogle ScholarPubMed
Jones, D. E., Buxbaum, L. U. and Scott, P. (2000). IL-4-independent inhibition of IL-12 responsiveness during Leishmania amazonensis infection. Journal of Immunology 165, 364–372.Google Scholar
Laird, R. M. and Hayes, S. M. (2009). Dynamics of CD3γε and CD3δε dimer expression during murine T cell development. Molecular Immunology 47, 582–589.Google Scholar
Lima, H. C., Bleyenberg, J. A. and Titus, R. G. (1997). A simple method for quantifying Leishmania in tissues of infected animals. Parasitology Today 13, 80–82.Google Scholar
Martinez Salazar, M. B., Delgado Dominguez, J., Silva Estrada, J., Gonzalez Bonilla, C. and Becker, I. (2014). Vaccination with Leishmania mexicana LPG induces PD-1 in CD8(+) and PD-L2 in macrophages thereby suppressing the immune response: a model to assess vaccine efficacy. Vaccine 32, 1259–1265.CrossRefGoogle Scholar
McGwire, B. S. and Satoskar, A. R. (2013). Leishmaniasis: clinical syndromes and treatment. QJM 107, 7–14.Google Scholar
McMahon-Pratt, D. and Alexander, J. (2004). Does the Leishmania major paradigm of pathogenesis and protection hold for New World cutaneous leishmaniases or the visceral disease? Immunological Reviews 201, 206–224.CrossRefGoogle ScholarPubMed
Mills, C. D., Kincaid, K., Alt, J. M., Heilman, M. J. and Hill, A. M. (2000). M-1/M-2 macrophages and the Th1/Th2 paradigm. Journal of Immunology 164, 6166–6173.Google Scholar
Murray, P. J., Allen, J. E., Biswas, S. K., Fisher, E. A., Gilroy, D. W., Goerdt, S., Gordon, S., Hamilton, J. A., Ivashkiv, L. B., Lawrence, T., Locati, M., Mantovani, A., Martinez, F. O., Mege, J. L., Mosser, D. M., Natoli, G., Saeij, J. P., Schultze, J. L., Shirey, K. A., Sica, A., Suttles, J., Udalova, I., van Ginderachter, J. A., Vogel, S. N. and Wynn, T. A., (2014). Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41, 14–20.Google Scholar
Pereira, B. A. and Alves, C. R. (2008). Immunological characteristics of experimental murine infection with Leishmania (Leishmania) amazonensis . Veterinary Parasitology 158, 239–255.CrossRefGoogle ScholarPubMed
Pinheiro, R. O. and Rossi-Bergmann, B. (2007). Interferon-gamma is required for the late but not early control of Leishmania amazonensis infection in C57Bl/6 mice. Memorias do Instituto Oswaldo Cruz 102, 79–82.Google Scholar
Qi, H., Ji, J., Wanasen, N. and Soong, L. (2004). Enhanced replication of Leishmania amazonensis amastigotes in gamma interferon-stimulated murine macrophages: implications for the pathogenesis of cutaneous leishmaniasis. Infection and Immunity 72, 988–995.Google Scholar
Qi, H., Popov, V. and Soong, L. (2001). Leishmania amazonensis-dendritic cell interactions in vitro and the priming of parasite-specific CD4(+) T cells in vivo . Journal of Immunology 167, 4534–4542.Google Scholar
Reimao, J. Q., Trinconi, C. T., Yokoyama-Yasunaka, J. K., Miguel, D. C., Kalil, S. P. and Uliana, S. R. (2013). Parasite burden in Leishmania (Leishmania) amazonensis-infected mice: validation of luciferase as a quantitative tool. Journal of Microbiological Methods 93, 95–101.CrossRefGoogle ScholarPubMed
Serafini, P., De Santo, C., Marigo, I., Cingarlini, S., Dolcetti, L., Gallina, G., Zanovello, P. and Bronte, V. (2004). Derangement of immune responses by myeloid suppressor cells. Cancer Immunology Immunotherapy 53, 64–72.Google Scholar
Serezani, C. H., Perrela, J. H., Russo, M., Peters-Golden, M. and Jancar, S. (2006). Leukotrienes are essential for the control of Leishmania amazonensis infection and contribute to strain variation in susceptibility. Journal of Immunology 177, 3201–3208.Google Scholar
Shultz, L. D. and Sidman, C. L. (1987). Genetically determined murine models of immunodeficiency. Annual Review Immunology 5, 367–403.CrossRefGoogle ScholarPubMed
Silveira, F. T., Lainson, R., De Castro Gomes, C. M., Laurenti, M. D. and Corbett, C. E. (2009). Immunopathogenic competences of Leishmania (V.) braziliensis and L. (L.) amazonensis in American cutaneous leishmaniasis. Parasite Immunology 31, 423–431.CrossRefGoogle ScholarPubMed
Soong, L. (2012). Subversion and utilization of host innate defense by Leishmania amazonensis . Frontiers in Immunology 3, 58.Google Scholar
Soong, L., Chang, C. H., Sun, J., Longley, B. J. Jr., Ruddle, N. H., Flavell, R. A. and McMahon-Pratt, D. (1997). Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection. Journal of Immunology 158, 5374–5383.Google Scholar
Teixeira, P. C., Velasquez, L. G., Lepique, A. P., de Rezende, E., Bonatto, J. M., Barcinski, M. A., Cunha-Neto, E. and Stolf, B. S. (2015). Regulation of Leishmania (L.) amazonensis protein expression by host T cell dependent responses: differential expression of oligopeptidase B, tryparedoxin peroxidase and HSP70 isoforms in amastigotes isolated from BALB/c and BALB/c nude mice. PLoS Neglected Tropical Diseases 9, e0003411.Google Scholar
Terabe, M., Kuramochi, T., Hatabu, T., Ito, M., Ueyama, Y., Katakura, K., Kawazu, S., Onodera, T. and Matsumoto, Y. (1999). Non-ulcerative cutaneous lesion in immunodeficient mice with Leishmania amazonensis infection. Parasitology International 48, 47–53.CrossRefGoogle ScholarPubMed
Wortis, H. H. (1971). Immunological responses of ‘nude’ mice. Clinical and Experimental Immunology 8, 305–317.Google Scholar
Supplementary material: Image

Velasquez supplementary material

Figure

Download Velasquez supplementary material(Image)
Image 69.7 KB
Supplementary material: Image

Velasquez supplementary material

Figure

Download Velasquez supplementary material(Image)
Image 1.7 MB
Supplementary material: Image

Velasquez supplementary material

Figure

Download Velasquez supplementary material(Image)
Image 359.1 KB