Experimental Rat Models in Induced Parasitic Infection: Inoculation Routes, Immune System Responses, and Seasonal Influences: A Review

Authors

Abstract

Experimental parasitology in laboratory rats has a long tradition, owing to the physiological proximity of the rat to humans and to the ease with which infection can be established under laboratory conditions. This review draws on work carried out over the past several decades and brings together three themes that the literature usually treats in isolation, although in practice they are deeply intertwined: the routes by which a parasite is introduced into the animal host; the immune mechanisms, early and late, that follow, comprising the rapid innate responses and the slower but more specific adaptive responses they instruct; and the influence that ambient temperature and seasonal variation exert on the strength and the direction of those responses. The parasites considered include Toxoplasma gondii, Leishmania species, Cryptosporidium parvum, Schistosoma japonicum, Fasciola hepatica, Strongyloidesratti and Echinococcus granulosus. A theme common to these organisms is that the mode of delivery, and therefore the anatomical setting of the first immunological encounter, can alter the character of the reaction: from a predominantly cellular to a predominantly humoral response, and from an acutely inflammatory to a more regulatory profile. The evidence likewise indicates a substantial seasonal variation in immune parameters, demonstrated experimentally in the published literature yet seldom reported in primary studies. The review closes with a call for greater attention to standardization, and to the explicit documentation of environmental conditions, in parasitological research that uses the rat as a model.

Keywords:

rat model, innate immunity, adaptive immunity, experimental parasitology, inoculation routes

DOI

https://doi.org/10.70604/10.70604/jmtbas.v3i2.220

References

1. World Health Organization. (2023). Neglected tropical diseases: Progress towards targets, 2023 update. WHO Press. https://www.who.int/publications/i/item/9789240081062

2. Iannaccone, P. M., & Jacob, H. J. (2009). Rats! Disease Models & Mechanisms, 2(5–6), 206–210. https://doi.org/10.1242/dmm.002733

3. Liesenfeld, O. (2002). Oral infection of C57BL/6 mice with Toxoplasma gondii: A new model of inflammatory bowel disease. Journal of Infectious Diseases, 185(Suppl. 1), S96–S101. https://doi.org/10.1086/338006

4. Nelson, R. J., & Demas, G. E. (1996). Seasonal changes in immune function. Quarterly Review of Biology, 71(4), 511–548. https://doi.org/10.1086/419555

5. Maizels, R. M., & McSorley, H. J. (2016). Regulation of the host immune system by helminth parasites. Journal of Allergy and Clinical Immunology, 138(3), 666–675. https://doi.org/10.1016/j.jaci.2016.07.007

6. He, Y., Zhang, Z., Xu, Y., Zhong, X., Zheng, H., Wu, Z., Lin, J., & Lu, K. (2021). Loss of natural resistance to schistosome in T cell deficient rat. PLOS Neglected Tropical Diseases, 15(1), e0009024. https://doi.org/10.1371/journal.pntd.0009024

7. Festing, M. F. W. (2010). The design and statistical analysis of animal experiments. ILAR Journal, 51(4), 312–322. https://doi.org/10.1093/ilar.51.4.312

8. Nair, M. G., Guild, K. J., & Artis, D. (2006). Novel effector molecules in type 2 inflammation: Lessons drawn from helminth infection and allergy. Journal of Immunology, 177(3), 1393–1399. https://doi.org/10.4049/jimmunol.177.3.1393

9. Yarovinsky, F. (2014). Innate immunity to Toxoplasma gondii infection. Nature Reviews Immunology, 14(2), 109–121. https://doi.org/10.1038/nri3598

10. Sacks, D., &Noben-Trauth, N. (2002). The immunology of susceptibility and resistance to Leishmania major in mice. Nature Reviews Immunology, 2(11), 845–858. https://doi.org/10.1038/nri933

11. Strikolcova, G., Filakovsky, D., Kadukova, M., Schreiberova, A., Klein, D., Halan, M., &Urbancikova, I. (2024). An immunocompetent intratracheal rat model susceptible to Cryptosporidium parvum and C. hominis. BMC Infectious Diseases, 24(1), 596. https://doi.org/10.1186/s12879-024-09500-z

12. Chauvin, A., Bouvet, G., &Boulard, C. (1995). Humoral and cellular immune responses to Fasciola hepatica experimental primary and secondary infection in sheep. International Journal for Parasitology, 25(10), 1227–1241. https://doi.org/10.1016/0020-7519(95)00052-5

13. Nair, M. G., Guild, K. J., Du, Y., Zaph, C., Yancopoulos, G. D., Valenzuela, D. M., Murphy, A., Stevens, S., Urban, J., & Artis, D. (2008). Goblet cell-derived resistin-like molecule beta augments CD4+ T cell production of IFN-gamma and infection-induced intestinal inflammation. Journal of Immunology, 181(7), 4709–4715. https://doi.org/10.4049/jimmunol.181.7.4709

14. Davoodi, J., Ghorbani, A., Nabavi, S. M., &Haghighat, S. (2020). Experimentally induced cerebral cystic echinococcosis in rats: A suitable animal model. Journal of Parasitology Research, 2020, 8842386. https://doi.org/10.1155/2020/8842386

15. Denkers, E. Y., &Gazzinelli, R. T. (1998). Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clinical Microbiology Reviews, 11(4), 569–588. https://doi.org/10.1128/CMR.11.4.569

16. Mestecky, J., Russell, M. W., & Elson, C. O. (2007). Intestinal IgA: Novel views on its function in the defence of the largest mucosal surface. Gut, 56(12), 1598–1607. https://doi.org/10.1136/gut.2007.128116

17. Cabral, G. A. (2005). Drugs of abuse, immune modulation, and AIDS. Journal of Neuroimmunology, 147(1–2), 5–9. https://doi.org/10.1016/j.jneuroim.2003.09.022

18. Murray, H. W., Berman, J. D., Davies, C. R., & Saravia, N. G. (2005). Advances in leishmaniasis. The Lancet, 366(9496), 1561–1577. https://doi.org/10.1016/S0140-6736(05)67629-5

19. Takeuchi, O., & Akira, S. (2010). Pattern recognition receptors and inflammation. Cell, 140(6), 805–820. https://doi.org/10.1016/j.cell.2010.01.022

20. Bogdan, C. (2001). Nitric oxide and the immune response. Nature Immunology, 2(10), 907–916. https://doi.org/10.1038/ni1001-907

21. Artis, D., & Spits, H. (2015). The biology of innate lymphoid cells. Nature, 517(7534), 293–301. https://doi.org/10.1038/nature14189

22. Butterworth, A. E. (1984). Cell-mediated damage to helminths. Advances in Parasitology, 23, 143–235. https://doi.org/10.1016/S0065-308X(08)60287-0

23. Mosmann, T. R., & Coffman, R. L. (1989). TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology, 7(1), 145–173. https://doi.org/10.1146/annurev.iy.07.040189.001045

24. Allen, J. E., & Wynn, T. A. (2011). Evolution of Th2 immunity: A rapid repair response to tissue destructive pathogens. PLOS Pathogens, 7(5), e1002003. https://doi.org/10.1371/journal.ppat.1002003

25. Hesse, M., Piccirillo, C. A., Belkaid, Y., Prufer, J., Mentink-Kane, M., Leusink, M., Cheever, A. W., Shevach, E. M., & Wynn, T. A. (2004). The pathogenesis of schistosomiasis is controlled by cooperating IL-10-producing innate effector and regulatory T cells. Journal of Immunology, 172(5), 3157–3166. https://doi.org/10.4049/jimmunol.172.5.3157

26. Anthony, R. M., Rutitzky, L. I., Urban, J. F., Stadecker, M. J., &Gause, W. C. (2007). Protective immune mechanisms in helminth infection. Nature Reviews Immunology, 7(12), 975–987. https://doi.org/10.1038/nri2199

27. Nally, J. E., Whitelegge, J. P., Aguilera, R., Pereira, M. M., Blanco, D. R., & Lovett, M. A. (2005). Purification and proteomic analysis of outer membrane vesicles from a clinical isolate of Leptospira interrogans serovar Copenhageni. Proteomics, 5(1), 144–152. https://doi.org/10.1002/pmic.200400880

28. Blanchard, N., & Bhatt, D. L. (2015). Control of Toxoplasma gondii by CD8 T cells. Journal of Immunology, 195(3), 937–944. https://doi.org/10.4049/jimmunol.1500481

29. Nelson, R. J., Demas, G. E., Klein, S. L., &Kriegsfeld, L. J. (2002). Seasonal patterns of stress, immune function, and disease. Cambridge University Press.

30. Carrillo-Vico, A., Lardone, P. J., Álvarez-Sánchez, N., Rodríguez-Rodríguez, A., & Guerrero, J. M. (2013). Melatonin: Buffering the immune system. International Journal of Molecular Sciences, 14(4), 8638–8683. https://doi.org/10.3390/ijms14048638

31. Karp, C. L. (2012). Unstressing intemperate models: How cold stress undermines mouse modeling. Journal of Experimental Medicine, 209(6), 1069–1074. https://doi.org/10.1084/jem.20120988

32. Dorny, P., Praet, N., Deckers, N., & Gabriel, S. (2009). Emerging food-borne parasites. Veterinary Parasitology, 163(3), 196–206. https://doi.org/10.1016/j.vetpar.2009.05.011

33. Pearce, E. J., & MacDonald, A. S. (2002). The immunobiology of schistosomiasis. Nature Reviews Immunology, 2(7), 499–511. https://doi.org/10.1038/nri843

34. National Research Council. (2011). Guide for the care and use of laboratory animals (8th ed.). National Academies Press. https://doi.org/10.17226/12910

35. Rostami, A., Riahi, S. M., Fakhri, Y., Saber, V., Hanifehpour, H., Valizadeh, S., Gholizadeh, M., Pour, B. M., &Pouya, R. H. (2018). The global seroprevalence of Toxoplasma gondii among wild boars: A systematic review and meta-analysis. Veterinary Parasitology, 257, 96–103. https://doi.org/10.1016/j.vetpar.2018.05.013

36. Livak, K. J., &Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262

37. Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M. T., Baker, M., Browne, W. J., Clark, A., Cuthill, I. C., Dirnagl, U., Emerson, M., Garner, P., Holgate, S. T., Howells, D. W., Karp, N. A., Lazic, S. E., Lidster, K., MacCallum, C. J., Macleod, M., … Würbel, H. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLOS Biology, 18(7), e3000410. https://doi.org/10.1371/journal.pbio.3000410

Published

2026-08-14
Statistics
Abstract Display: 0
PDF Downloads: 0

How to Cite

Ihsan, K. A. A. (2026). Experimental Rat Models in Induced Parasitic Infection: Inoculation Routes, Immune System Responses, and Seasonal Influences: A Review. Journal of Modern Techniques in Biology and Allied Sciences, 3(2), 89-99. https://doi.org/10.70604/10.70604/jmtbas.v3i2.220

Issue

Section

Articles

How to Cite

Ihsan, K. A. A. (2026). Experimental Rat Models in Induced Parasitic Infection: Inoculation Routes, Immune System Responses, and Seasonal Influences: A Review. Journal of Modern Techniques in Biology and Allied Sciences, 3(2), 89-99. https://doi.org/10.70604/10.70604/jmtbas.v3i2.220