Experimental Rat Models in Induced Parasitic Infection: Inoculation Routes, Immune System Responses, and Seasonal Influences: A Review
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 routesDOI
https://doi.org/10.70604/10.70604/jmtbas.v3i2.220References
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
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