Comparison Between Immuno-Clinicopathological Features of Experimental and Human Visceral Leishmaniasis by Leishmania donovani

Abstract

Background

Current understanding of visceral leishmaniasis (VL) depends upon the experimental model. Different species of mouse and hamster have been used as model for VL. It is already evident that the mouse model of VL is not a true reflection of the pathology of human visceral leishmaniasis (HuVL). On the other hand, hamster is reported to be a better model of VL to study the progressive as well as chronic pathology of the disease.

Objective

To compare immuno-clinicopathological features of experimental VL (ExVL) and HuVL by Leishmania donovani.

Methods

Hamsters were infected (15 and 60 days) and their immunological, clinical and biochemical parameters were compared with the cases of HuVL.

Results

Splenomegaly and hepatomegaly were observed in infected hamster post-infection, which are hallmarks of symptomatic HuVL cases. Clinical, biochemical and pathological manifestations of infected hamsters were consistent with that of HuVL cases, except parameters such as body weight, uric acid, alkaline phosphatase and random glucose. The absence of clear dichotomy between pro- and anti-inflammatory cytokines was also observed after infection at different sites of infection.

Conclusion

Our results suggest that the golden hamster (Mesocricetus auratus), infected via the intracardiac route, constitutes a very good model for the study of experimental Leishmania donovani infections. However, certain differences in clinical presentations of infected hamsters (via intracardiac route) with HuVL suggest further optimization of this animal model like route of infection such as intradermal, which is more close to natural infection.

Graphical abstract

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. 1.

    National Vector Borne Disease Control Programme (2018) KALA-AZAR. http://www.nvbdcp.gov.in/kala-new.html. Accessed 28 Nov 2018

  2. 2.

    Carrión J, Nieto A, Iborra S, Iniesta V, Soto M, Folgueira C, Abanades DR, Requena JM, Alonso C (2006) Immunohistological features of visceral leishmaniasis in BALB/c mice. Parasite Immunol 28(5):173–183

    Article  Google Scholar 

  3. 3.

    das Dores Moreira N et al (2012) Parasite burden in hamsters infected with two different strains of Leishmania (Leishmania) infantum: “Leishman Donovan Units” versus real-time PCR. PLoS One 7(10):e47907. https://doi.org/10.1371/journal.pone.0047907

    CAS  Article  Google Scholar 

  4. 4.

    Smelt SC, Engwerda CR, McCrossen M, Kaye PM (1997) Destruction of follicular dendritic cells during chronic visceral leishmaniasis. J Immunol 158(8):3813–3821

    CAS  PubMed  Google Scholar 

  5. 5.

    Murray HW, Masur H, Keithly JS (1982) Cell-mediated immune response in experimental visceral leishmaniasis. I. Correlation between resistance to Leishmania donovani and lymphokine-generating capacity. J Immunol 129(1):344–350

    CAS  PubMed  Google Scholar 

  6. 6.

    Murray HW (1997) Endogenous interleukin-12 regulates acquired resistance in experimental visceral leishmaniasis. J Infect Dis 175(6):1477–1479

    CAS  Article  Google Scholar 

  7. 7.

    Squires KE, Schreiber RD, McElrath MJ, Rubin BY, Anderson SL, Murray HW (1989) Experimental visceral leishmaniasis: role of endogenous IFN-g in host defense and tissue granulomatous response. J Immunol 143(12):4244–4249

    CAS  PubMed  Google Scholar 

  8. 8.

    Rai AK, Thakur CP, Singh A, Seth T, Srivastava SK, Singh P, Mitra DK (2012) Regulatory T cells suppress T cell activation at the pathologic site of human visceral leishmaniasis. PLoS One 7(2):e31551. https://doi.org/10.1371/journal.pone.0031551

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Singh OP, Gidwani K, Kumar R, Nylén S, Jones SL, Boelaert M, Sacks D, Sundar S (2012) Reassessment of immune correlates in human visceral leishmaniasis as defined by cytokine release in whole blood. Clin Vaccine Immunol 19(6):961–996. https://doi.org/10.1128/CVI.00143-12

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Melby PC, Chandrasekar B, Zhao W, Coe JE (2001) The hamster as a model of human visceral leishmaniasis: progressive disease and impaired generation of nitric oxide in the face of a prominent Th1-like cytokine response. J Immunol 166(3):1912–1920. https://doi.org/10.4049/jimmunol.166.3.1912

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Moreira ND, Vitoriano-Souza J, Roatt BM, Vieira PM, Coura-Vital W, Cardoso JM, Rezende MT, Ker HG, Giunchetti RC, Carneiro CM, Reis AB (2016) Clinical, hematological and biochemical alterations in hamster (Mesocricetus auratus) experimentally infected wit Leishmania infantum through different routes of inoculation. Parasite Vector. https://doi.org/10.1186/s13071-016-1464-y

    Article  Google Scholar 

  12. 12.

    Moreno J, Alvar J (2002) Canine leishmaniasis: epidemiological risk and the experimental model. Trends Parasitol 89(9):399–405. https://doi.org/10.1016/S1471-4922(02)02347-4

    Article  Google Scholar 

  13. 13.

    Chunge CN et al (1989) A rapid staining technique for Leishmania parasites in splenic aspirate smears. Ann Trop Med Parasitol 83(4):361–364

    CAS  Article  Google Scholar 

  14. 14.

    Tiwari P, Verma P, Kureel AK, Saini S, Rai AK (2016) Pi inhibits intracellular accumulation of methylglyoxal in promastigote form of L. donovani. Mol Biochem Parasitol 207:89–95. https://doi.org/10.1016/j.molbiopara.2016.06.005

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Dube A, Singh N, Sundar S (2005) Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persist in in vitro and in vivo experimental models. Parasitol Res 96:216–223. https://doi.org/10.1007/s00436-005-1339-1

    Article  PubMed  Google Scholar 

  16. 16.

    Jaffe CL, Rachamim N (1989) Amastigote stage-specific monoclonal antibodies against Leishmania major. Infect Immun 57(12):3770–3777

    CAS  Article  Google Scholar 

  17. 17.

    Sindhu KJ, Kureel AK, Saini S, Kumari S, Verma P, Rai AK (2018) Characterization of phosphate transporter(s) and understanding their role in Leishmania donovani parasite. Acta Parasitol 63(1):75–88. https://doi.org/10.1515/ap-2018-0009

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Fan H, Gulley ML (2001) DNA extraction from fresh or frozen tissues. In: Killeen AA (ed) Molecular pathology protocols methods in Molecular Medicine™, vol 49. Humana Press, Totowa, pp 5–10

    Google Scholar 

  19. 19.

    Verma S, Kumar R, Katara GK, Singh LC, Negi NS, Ramesh V, Salotra P (2010) Quantification of parasite load in clinical samples of leishmaniasis patients: IL-10 level correlates with parasite load in visceral leishmaniasis. PLoS One 5(4):e10107. https://doi.org/10.1371/journal.pone.0010107

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Facchini F, Chen YDI, Hollenbeck CB, Reaven GM (1991) Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance and plasma uric acid concentration. J Am Med Assoc 266(21):3008–3011

    CAS  Article  Google Scholar 

  21. 21.

    Vroon DH, Israili Z (1990) Alkaline phosphatase and gamma glutamyltransferase. In: Walker HK, Hall WD, Hurst JW (eds) Clinical methods: the history, physical, and laboratory examinations, 3rd edn. Butterworths, Boston

    Google Scholar 

  22. 22.

    Aslan H, Dey R, Meneses C, Castrovinci P, Jeronimo SM, Oliva G, Fischer L, Duncan RC, Nakhasi HL, Valenzuela GJ, Kamhawi S (2013) A new model of progressive visceral leishmaniasis in hamsters by natural transmission via bites of vector sand flies. J Infect Dis 207:1328–1338. https://doi.org/10.1093/infdis/jis932

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank all the patients and control subjects who volunteered to participate in this study. We are thankful to the Council of Scientific and Industrial Research-Central Drug Research Institute (CSIR-CDRI) Lucknow, India, for providing animal house facility. We acknowledge Central Facility, M.N.N.I.T. Allahabad, India, for allowing us to use real-time PCR (qPCR). We also thank the Council of Scientific and Industrial Research (CSIR), Government of India, for providing fellowship to Ms. Sheetal Saini (09/1032(0006)/2015-EMR-1).

Funding

This work was supported by the Department of Science and Technology, Government of India, Science and Engineering Research Board (Ref no. SB/YS/LS-234/2013 Dated 15/05/2014) and Department of Biotechnology, Ministry of Science and Technology, Government of India (Ref. no. BT/PR14154/MED/29/965/2015 Dated 15/03/2017).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Ambak Kumar Rai.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 324 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Saini, S., Dube, A., Sahasrabuddhe, A.A. et al. Comparison Between Immuno-Clinicopathological Features of Experimental and Human Visceral Leishmaniasis by Leishmania donovani. Acta Parasit. 65, 57–67 (2020). https://doi.org/10.2478/s11686-019-00127-8

Download citation

Keywords

  • Visceral leishmaniasis
  • Leishmania donovani
  • Experimental model
  • Mesocricetus auratus
  • Human visceral leishmaniasis
  • Immuno-clinicopathological features