OJVM  Vol.5 No.5 , May 2015
Phenotypic Characterization of the Response to Infection with Trichinella spiralis in Genetically Defined Mouse Lines of the CBi-IGE Stock
Abstract: Trichinella spiralis (T. spiralis), which is a cosmopolitan nematode that infects humans among other species, presents a complex host-parasite relationship that hinders the development of tools to eradicate the parasitosis. The aim of this research was to analyze the host response during a primary infection with T. spiralis in five genetically different mouse lines of the CBi-IGE stock. Adult males from the CBi+, CBi−, CBi, CBi/L and CBi/C lines were infected with 1, 2 or 4 L1 larvae per g of body weight. In the chronic stage, the number of parasites per g of tissue (relative larval load, rLL) showed a significant host genotype-dose interaction, since it did not increase in the same way in the five genotypes. At the lowest dose, both CBii− and CBi/L mice were resistant while CBi+, CBi/C, and CBi were susceptible. At the highest dose, only CBi/L remained resistant, and CBi+ was the most susceptible. The reproductive capacity index of adult worms (RCI = rLL/infective dose) evinced only a genotype effect, allowing rating each line as resistant or susceptible regardless of dose. Animals receiving 2 L1 larvae were also sacrificed in the intestinal phase (6 and 13 days p-i) to determine the number of adult parasites (nAP) recovered in a small intestine segment, and female fecundity (Ff). No differences in nAP were observed among genotypes on day 6 p-i. nAP decreased between days 6 and 13 p-i, this reduction being different among genotypes and significant only in CBi/L and CBi/C. Ff decreased in CBi/L and CBi/C on day 13 p-i. At the time of infection, serum cytokine baseline values showed a Th1 orientation for genotype CBi/L (high IFN-γ and IL-2) and a Th2 for CBi+ (high IL-4 and IL-10).The variability in the response observed in this murine model suggests its potential usefulness to gain insight into the mechanisms that regulate host-parasite relationship.
Cite this paper: Vasconi, M. , Bertorini, G. , Codina, A. , Indelman, P. , Masso, R. , Hinrichsen, L. (2015) Phenotypic Characterization of the Response to Infection with Trichinella spiralis in Genetically Defined Mouse Lines of the CBi-IGE Stock. Open Journal of Veterinary Medicine, 5, 111-122. doi: 10.4236/ojvm.2015.55015.

[1]   Calcagno, M.A., Teixeira, C., Forastiero, M.A., Costantino, S.N. and Venturiello, S.M. (2005) Clinical, Serological and Parasitological Aspects of an Outbreak of Human Trichinellosis in Villa Mercedes, San Luis, Argentina. The Acute and Chronic Phases of the Infection. Medicina, 65, 302-306.

[2]   Gottstein, B., Pozio, E. and Nöckler, K. (2009) Epidemiology, Diagnosis, Treatment, and Control of Trichinellosis. Clinical Microbiology Reviews, 22, 127-145.

[3]   Artis, D. (2006) New Weapons in the War on Worms: Identification of Putative Mechanisms of Immune-Mediated Expulsion of Gastrointestinal Nematodes. International Journal for Parasitology, 36, 723-733.

[4]   Vasconi, M.D., Malfante, P., Bassi, A., Giudici, C., Revelli, S., Di Masso, R., Font, M.T. and Hinrichsen, L. (2008) Phenotypic Differences on the Outcome of the Host-Parasite Relationship: Behavior of Mice of the CBi Stock in Natural and Experimental Infections. Veterinary Parasitology, 153, 157-163.

[5]   Gray, G.D. and Gill, H.S. (1993) Host Genes, Parasites and Parasitic Infections. International Journal for Parasitology, 23, 485-494.

[6]   Di Masso, R.J., Abdala, S., Sanchez, S.M. and Font, M.T. (1991) Respuesta a la selección divergente por conformación corporal en el ratón. Mendeliana, 9, 79-92.

[7]   Hinrichsen, L.I. and Di Masso, R.J. (2010) Use of a Murine Model Original of Argentina to Characterize Complex Phenotypes. Journal of Basic and Applied Genetics, 21, 1-12.

[8]   Guide for the Care and Use of Laboratory Animals (2011) National Research Council. 8th Edition, The National Academies Press, Washington DC.

[9]   Luebke, R.W. (2007) Nematodes as Host Resistance Models for Detection of Immunotoxicity. Methods, 41, 38-47.

[10]   Perrudet-Badoux, A., Binaghi, R.A. and Biozzi, G. (1975) Trichinella Infestation in Mice Genetically Selected for High and Low Antibody Production. Immunology, 29, 387-390.

[11]   Perrudet-Badoux, A., Binaghi, R.A. and Boussac-Aron, Y. (1978) Trichinella spiralis Infection in Mice. Mechanism of the Resistance in Animals Genetically Selected for High and Low Antibody Production. Immunology, 35, 519-522.

[12]   Reiterová, K., Antolová, D. and Hurníková, Z. (2009) Humoral Immune Response of Mice Infected with Low Doses of Trichinella spiralis Muscle Larvae. Veterinary Parasitology, 159, 232-235.

[13]   Martínez-Gómez, F., Fuentes-Castro, B.E. and Bautista-Garfias, C.R. (2011) The Intraperitoneal Inoculation of Lactobacillus casei in Mice Induces Total Protection against Trichinella spiralis Infection at Low Challenge Doses. Parasitology Research, 109, 1609-1617.

[14]   Leclair, D., Forbes, L.B., Suppa, S. and Gajadhar, A.A. (2003) Evaluation of a Digestion Assay and Determination of Sample Size and Tissue for the Reliable Detection of Trichinella Larvae in Walrus Meat. Journal of Veterinary Diagnostic Investigation, 15,188-191.

[15]   Kapel, C.M.O. and Gamble, H.R. (2000) Infectivity, Persistence, and Antibody Response to Domestic and Sylvatic Trichinella spp. in Experimentally Infected Pigs. International Journal for Parasitology, 30, 215-221.

[16]   Dvorozňáková, E., Hurníková, Z. and Kolodziej-Sobocińska, M. (2011) Development of Cellular Immune Response of Mice to Infection with Low Doses of Trichinella spiralis, Trichinella britovi and Trichinella pseudospiralis Larvae. Parasitology Research, 108, 169-176.

[17]   Sheskin, D.J. (2011) Handbook of Parametric and Non-Parametric Statistical Procedures. 5th Edition, Chapman & Hall/CRC, London.

[18]   Tatsuoka, M. (1971) Multivariate Analysis. Techniques for Educational and Psychological Research. John Wiley and Sons Inc., New York.

[19]   Taylor, M.D., Betts, C.J. and Else, K.J. (2000) Peripheral Cytokine Responses to Trichuris muris Reflect Those Occurring Locally at the Site of Infection. Infection and Immunity, 68, 1815-1819.

[20]   Peters, L.L., Robledo, R.F., Bult, C.J., Churchill, G.A., Paigen, B.J. and Svenson, K.L. (2007) The Mouse as a Model for Human Biology: A Resource Guide for Complex Trait Analysis. Nature Reviews Genetics, 8, 58-69.

[21]   Longley, R., Smith, C., Fortin, A., Berghout, J., McMorran, B., Burgio, G., Foote, S. and Gros, P. (2011) Host Resistance to Malaria: Using Mouse Models to Explore the Host Response. Mammalian Genome, 22, 32-42.

[22]   Blackwell, N.M. and Else, K.J. (2002) A Comparison of Local and Peripheral Parasite-Specific Antibody Production in Different Strains of Mice Infected with Trichuris muris. Parasite Immunology, 24, 203-211.

[23]   Filbey, K.J., Grainger, J.R., Smith, K.A., Boon, L., van Rooijen, N., Harcus, Y., Jenkins, S., Hewitson, J.P. and Maizels, R.M. (2014) Innate and Adaptive Type 2 Immune Cell Responses in Genetically Controlled Resistance to Intestinal Helminth Infection. Immunology and Cell Biology, 92, 436-448.

[24]   Kobets, T., Havelková, H., Grekov, I., Volkova, V., Vojtísková, J., et al. (2012) Genetics of Host Response to Leishmania Tropica in Mice—Different Control of Skin Pathology, Chemokine Reaction, and Invasion into Spleen and Liver. PLoS Neglected Tropical Diseases, 6, e1667.

[25]   Vasilev, S., Gruden-Movsesijan, A., Ilic, N. and Sofronic-Milosavljevic, L.J. (2009) Strain Difference in Susceptibility to Trichinella spiralis Infection between Dark Agouti and Albino Oxford Rats. Veterinary Parasitology, 159, 229-231.

[26]   Bell, R.G. (1988) Genetic Analysis of Expulsion of Adult Trichinella spiralis in NFS, C3H/He, and B10.BR Mice. Experimental Parasitology, 66, 57-65.

[27]   Ishikawa, N., Goyal, P.K., Mahida, Y.R., Li, K.F. and Wakelin, D. (1998) Early Cytokine Responses during Intestinal Parasitic Infections. Immunology, 193, 257-263.

[28]   Dehlawi, M.S. and Goyal, P.K. (2003) Responses of Inbred Mouse Strains to Infection with Intestinal Nematodes. Journal of Helminthology, 77, 119-124.

[29]   Dvorozňáková, E., Kolodziej-Sobocińska, M. and Hurníková, Z. (2012) Trichinella spiralis Reinfection: Changes in Cellular and Humoral Immune Response in BALB/c Mice. Helminthologia, 49, 201-210.

[30]   Teunis, P.F., Koningstein, M., Takumi, K. and van der Giessen, J.W. (2012) Human Beings Are Highly Susceptible to Low Doses of Trichinella spp. Epidemiology Infection, 140, 210-218.

[31]   Marti, H.P. and Murrell, K.D. (1986) Trichinella spiralis: Antifecundity and Antinewborn Larvae Immunity in Swine. Experimental Parasitology, 62, 370-375.

[32]   Hashimoto, K., Uchikawa, R., Tegoshi, T., Takeda, K., Yamada, M. and Arizono, N. (2010) Immunity-Mediated Regulation of Fecundity in the Nematode Heligmosomoides polygyrus—The Potential Role of Mast Cells. Parasitology, 137, 881-887.

[33]   Lawrence, C.E. (2003) Is There a Common Mechanism of Gastrointestinal Nematode Expulsion? Parasite Immunology, 25, 271-281.

[34]   Maizels, R.M., Pearce, E.J., Artis, D., Yazdanbakhsh, M. and Wynn, T.A. (2009) Regulation of Pathogenesis and Immunity in Helminth Infections. Journal of Experimental Medicine, 206, 2059-2066.

[35]   Knight, P.A., Brown, J.K. and Pemberton, A.D. (2008) Innate Immune Response Mechanisms in the Intestinal Epithelium: Potential Roles for Mast Cells and Goblet Cells in the Expulsion of Adult Trichinella spiralis. Parasitology, 135, 655-670.

[36]   Bell, R.G., Adams, L.S. and Ogden, R.W. (1984) A Single Gene Determines Rapid Expulsion of Trichinella spiralis in Mice. Infection and Immunity, 45, 273-275.

[37]   Bell, R.G. and Liu, W.M. (1988) Trichinella spiralis: Quantitative Relationships between Intestinal Worm Burden, Worm Rejection, and the Measurement of Intestinal Immunity in Inbred Mice. Experimental Parasitology, 66, 44-56.

[38]   Gentilini, M.V., Nuñez, G.G., Roux, M.E. and Venturiello, S.M. (2011) Trichinella spiralis Infection Rapidly Induces Lung Inflammatory Response: The Lung as the Site of Helminthocytotoxic Activity. Immunobiology, 216, 1054-1063.

[39]   Gause, W.G., Urban Jr., J.F. and Stadecker, M.J. (2003) The Immune Response to Parasitic Helminths: Insights from Murine Models. Trends in Immunology, 24, 269-277.

[40]   Hsieh, C.-S., Macatonia, S.E., O’Garra, A. and Murphy, K.M. (1995) T Cell Genetic Background Determines Default T Helper Phenotype Development in Vitro. Journal of Experimental Medicine, 181, 713-721.