Abstract
The main objective of this study was to determine whether a chemical immunomodulation protocol could reduce the resistance of NOD/LtSz-SCID mice to Plasmodium falciparum infection and provide an improved mouse model for screening the antimalarial activity of new compounds. This model was compared with the presently used immunodeficient Beige/Nude/Xid (BNX) mouse model, using the same protocol, in terms of percentage of infected mice, parasite development, leukocyte response and phagocytosis of P. falciparum infected cells in various organs. Our results show that the combination of the chemical immune modulation protocol with the genetic background of NOD/LtSz-SCID mice results in the development of long-lasting P. falciparum infection in a high percentage of mice. A comparison of the results obtained in the histological study for both mouse models suggests that the higher rate of success in NOD/LtSz-SCID mice could be related to the reduced macrophage recruitment developed in different tissues to remove the parasite from blood.
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References
Abdalla SH (1990) Hematopoiesis in human malaria. Blood Cells 16:401–416
Badell E, Pasquetto V, van Rooijen N, Druilhe P (1995) A mouse model for human malaria erythrocytic stages. Parasitol Today 11:235–237
Badell E, Oeuvray C, Moreno A, Soe S, Van Rooijen N, Bouzidi A, Druilhe P (2000) Human malaria in immunocompromised mice: an in vivo model to study defense mechanisms against Plasmodium falciparum. J Exp Med 192:1653–1660
Celada A, Cruchaud A, Perrin LH (1983) Phagocytosis of Plasmodium falciparum-parasitized erythrocytes by human polymorphonuclear leukocytes. J Parasitol 69:49–53
Duarte MI, Corbett CE, Boulos M, Amato Neto V (1985) Ultrastructure of the lung in falciparum malaria. Am J Trop Med Hyg 34:31–35
Ishihara C, Hiratai R, Tsuji M, Yagi K, Nose M, Azuma I (1998) Mannan decelerates the clearance of human red blood cells in SCID mouse. Immunopharmacology 38:223–228.
Moore JM, Kumar N, Shultz LD, Rajan TV (1995) Maintenance of the human malarial parasite, Plasmodium falciparum, in SCID mice and transmission of gametocytes to mosquitoes. J Exp Med 181:2265–2270
Moreno A, Badell E, Van Rooijen N, Druilhe P (2001) Human malaria in immunocompromised mice: new in vivo model for chemotherapy studies. Antimicrob Agents Chemother 45:1847–1853
Prins JB, Todd JA, Rodrigues NR, Ghosh S, Hogarth PM, Wicker LS, Gaffney E, Podolin PL, Fischer PA, Sirotina A (1993) Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice. Science 260:695–698
Rooijen N van, Sanders A (1994) Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods 174:83–93
Rubio JM, Benito A, Roche J, Berzosa PJ, Garcia ML, Mico M, Edu M, Alvar J (1999) Semi-nested, multiplex polymerase chain reaction for detection of human malaria parasites and evidence of Plasmodium vivax infection in Equatorial Guinea. Am J Trop Med Hyg 60:183–187
Schwarzer E, Turrini F, Ulliers D, Giribaldi G, Ginsburg H, Arese P (1992) Impairment of macrophage functions after ingestion of Plasmodium falciparum-infected erythrocytes or isolated malarial pigment. J Exp Med 176:1033–1041
Serreze DV, Gaedeke JW, Leiter EH (1993a) Hematopoietic stem-cell defects underlying abnormal macrophage development and maturation in NOD/Lt mice: defective regulation of cytokine receptors and protein kinase C. Proc Natl Acad Sci U S A 90:9625–9629
Serreze DV, Gaskins HR, Leiter EH (1993b) Defects in the differentiation and function of antigen presenting cells in NOD/Lt mice. J Immunol 150:2534–2543
Seydel KB, Stanley SLJr (1996) SCID mice and the study of parasitic disease. Clin Microbiol Rev 9:126–134
Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB, Tennent B, Mckenna S, Mobraaten L, Rajan TV, Greiner DL (1995) Multiple defects in innate and adaptive immunologic function in NOD/LtSz-SCID mice. J Immunol 154:180–191
Tacchini-Cottier F, Zweifel C, Belkaid Y, Mukankundiye C, Vasei M, Launois P, Milon G, Louis JA (2000) An immunomodulatory function for neutrophils during the induction of a CD4+ Th2 response in BALB/c mice infected with Leishmania major. J Immunol 165:2628–2636
Taramelli D, Basilico N, Pagani E, Grande R, Monti D, Ghione M, Olliaro P (1995) The heme moiety of malaria pigment (beta-hematin) mediates the inhibition of nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages. Exp Parasitol 81:501–511
Tsuji M, Ishihara C, Arai S, Hiratai R, Azuma I (1995) Establishment of a SCID mouse model having circulating human red blood cells and a possible growth of Plasmodium falciparum in the mouse. Vaccine 13:1389–1392
Turrini F, Schwarzer E, Arese P (1993) The involvement of hemozoin toxicity in depression of cellular immunity. Parasitol Today 9:297–300
Walsh PS, Metzger DA, Higuchi R (1991) Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques 10:506–513
Acknowledgements
We thank Ana Maria Aransay, Dario Cabanes, Elizabeth Ferrer, Edurne Laurin and Maria Jesus Perteguer for their contributions. We also thank the Retrovirus Diagnosis Unit of the Instituto de Salud Carlos III for blood supplies. This work has been supported by the Research Network of Tropical Disease Centres in Spain (RICET), by the Intramural Programme from the Instituto de Salud Carlos III (Expedient 03/11) and by a grant from the Seneca Foundation from the Autonomous Community of Murcia. The experiments comply with the current laws of the country in which they were performed.
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Moreno Sabater, A., Moreno, M., Moreno, F.J. et al. Experimental infection of immunomodulated NOD/LtSz-SCID mice as a new model for Plasmodium falciparum erythrocytic stages. Parasitol Res 95, 97–105 (2005). https://doi.org/10.1007/s00436-004-1249-7
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DOI: https://doi.org/10.1007/s00436-004-1249-7