Effect of albendazole therapy on susceptible and resistant Haemonchus contortus larvae in Mongolian gerbils (Meriones unguiculatus) and distribution of inflammatory cells in the stomach wall

Open access

Abstract

The effect of albendazole therapy on the reduction of drugsusceptible and drug-resistant strains of Haemonchus contortus larvae on day 10 post infection (p.i.), distribution and the relative numbers of innate immunity cells — eosinophils/neutrophils and mast cells in the stomach wall of immunosupressed Mongolian gerbils on days 4/1, 7/4, 10/7 and 14/11 post infection/post therapy (p.i./p.t.) were investigated in the present study. The efficacy of albendazole was significantly lower on benzimidazole (BZ) resistant larvae (L3 and L4 stages) (58.92 %) than the efficacy on susceptible strain of larvae (94.15 %). H. contortus infection elicited strong inflammation in mucosal and submucosal layers of the stomach, where mucosal mast cells MMC) were in the highest numbers in the lamina propria mucosae on day 7/4 p.i./p.t. Reduction of larval numbers following treatment resulted in a gradual decrease of MMC and connective tissue mast cells (CTMC). The lower counts of CTMC in the submucosa were seen in gerbils infected with BZ-susceptible strain during the whole period post therapy. In case of infection with BZ-resistant strain, peroxidase containig cells (eosinophils) peaked on day 7/4 p.i./p.t., whereas infection with BZ-susceptible strain elicited massive accumulation of these cells on day 4/1 p.i./p.t., particularly in the submucosa. No marked differences in eosinophils localisation were observed between both groups after the therapy. Goblet cells were found only in the proximal parts of glandulae gastricae close to the mucosal surface and no differences in the distribution in the stomach wall of both groups of animals were observed. After therapy the higher larval counts in case of BZ-resistant strain were in the correlation with the lower decline of CTMC and eosinophils, but MMC numbers were not significantly different between both treated groups. Present data indicate that in early stage post infection, the distribution of individual innate immunity cells might be directly affected by the larvae, and that the genetic and consequently biological differences related to the resistance to benzimidazoles probably had the impact on the interactions of larvae with the different immune cells in their niche.

[1] Balic, A., Bowles, V. M., Meeusen, E. N. (2000): The immunobiology of gastrointestinal nematode infections in ruminants. Adv. Parasitol., 45: 181–241 http://dx.doi.org/10.1016/S0065-308X(00)45005-0

[2] Conder, G. A., Jen, L. W., Marbury, K. S., Johnson, S. S., Guimond, P. M., Thomas, E. M., Lee, B. L. (1990): A novel anthelmintic model utilizing jirds Meriones unguiculatus, infected with Haemonchus contortus. J. Parasitol., 76(2): 168–170. DOI: 10.2307/3283008 http://dx.doi.org/10.2307/3283008

[3] Conder, G. A., Johnson, S. S., Guimond, P. M., Cox, D. L., Lee, B. L. (1991): Concurrent infections with the ruminant nematodes Haemonchus contortus and Trichostrongylus colubriformis in jirds Meriones unguiculatus and use of this model for anthelmintic studies. J. Parasitol., 77(4): 621–623 http://dx.doi.org/10.2307/3283169

[4] Conder, G. A., Johnson, S. S., Hall, A. D., Fleming, M. W., Mills, M. D., Guimond, P. M. (1992): Growth and development of Haemonchus contortus in jirds Meriones unguiculatus. J. Parasitol., 78(3): 492–497 http://dx.doi.org/10.2307/3283650

[5] Dale, M. M., Foreman, J.C., Fan, Tai-ping, D. (1994): Textbook of immunopharmacology. 3rd Edition, Oxford, UK, Blackwell Scientific publication, 63p.

[6] Enerback, L. (1966): Mast cells in rat gastrointestinal mucosa. I. Effects of fixation. Acta Pathol. Microbiol. Csand., 66(3): 289–302

[7] Enerback, L. (1981): The gut mast cell. Monogr. Allergy, 17: 222–232

[8] Featherston, D. W., Wakelin, D., Lammas, D. A. 1992): Inflammatory responses in the intestine during tapeworm infections. Mucosal mast cells and mucosal mast cell proteases in Sprague-Dawley rats infected with Hymenolepis diminuta. Int. J. Parasitol., 22(7): 961–966 http://dx.doi.org/10.1016/0020-7519(92)90054-O

[9] Gaba, S., Cabaret, J., Sauvé, C., Cortet, J., Silvestre, A. (2010): Experimental and modeling approaches to evaluate different aspects of the efficacy of targeted selective treatment of anthelmintics against sheep parasite nematodes. Vet. Parasitol., 171(3 — 4): 254–262. DOI: 10.1016/j.vetpar.2010.03.040 http://dx.doi.org/10.1016/j.vetpar.2010.03.040

[10] Geary, T. G., Conder, G. A., Bishop, B. (2004): The changing landscape of antiparasitic drug discovery for veterinary medicine. Trends. Parasitol., 20(10): 449–455. DOI: 10.1016/j.pt.2004.08.003 http://dx.doi.org/10.1016/j.pt.2004.08.003

[11] González, I. C., Davis, L. N., Smith, I. C. K. (2004): Novel thiophenes and analogues with anthelmintic activity against Haemonchus contortus. Bioorg. Med. Chem. Lett., 14(15): 4037–4043. DOI: 10.1016/j.bmcl.2004.05.044 http://dx.doi.org/10.1016/j.bmcl.2004.05.044

[12] Hubert, J., Kerboeuf, D. (1984): A new method for culture of larvae used in diagnosis of ruminant gastrointestinal strongylosis: comparison with faecal cultures. Can. J. Comp. Med., 48(1): 63–71

[13] Hunyady, B., Krempels, K., Harta, G., Mezey, E. 1996): Immunohistochemical signal implification by catalyzed reporter deposition and its application in double immunostaining. J. Histochem. Cytochem., 44(12):1353–1362. DOI: 10.1177/44.12.8985127 http://dx.doi.org/10.1177/44.12.8985127

[14] Hrčková, G., Velebný, S., Daxnerová, Z., Solár, P. 2006): Praziquantel and liposomized glucan-treatment modulated liver fibrogenesis and mastocytosis in mice infected with Mesocestoides vogae (M. corti, Cestoda) tetrathyridia. Parasitology, 132(4): 581–594. DOI: 10.1017/S0031182005009364 http://dx.doi.org/10.1017/S0031182005009364

[15] Johnson, S. S., Coscarelli, E. M., Davis, J. P., Zaya, R. M., Day, J. S., Barsuhn, C. L., Martin, R. A., Vidmar, T. J., Lee, B. H., Conder, G. A., Geary, T. G., Ho, N. F. H., Thompson, D. P. (2004): Interrelationships among physicochemical properties, absorption and anthelmintic activities of 2-desoxoparaherquamide and selected analogs. J. Vet. Pharmacol. Therap., 27(3): 169–181. DOI: 10.1111/j.1365-2885.2004.00577 http://dx.doi.org/10.1111/j.1365-2885.2004.00577.x

[16] Khan, A. I., Horii, Y., Tiuria, R., Sato, Y., Nawa, Y. 1993): Mucosal mast cells and the expulsive mechanisms of mice against Strongyloides venezuelensis. I. J. Parasitol., 23(5): 551–555

[17] Knox, D. P., Jones, D. G. (1990): Studies on the presence and release of proteolyticenzymes (proteinases) in gastrointestinal nematodes of ruminants. Int. J. Parasitol., 20(2): 243–249. DOI: 10.1016/0020-7519(90)90106-W http://dx.doi.org/10.1016/0020-7519(90)90106-W

[18] Königová, A., Hrčková, G., Velebný, S., Čorba, J., Várady, M. (2008): Experimental infection of Haemonchus contortus strains resistant and susceptible to benzimidazoles and the effect on mast cells distribution in the stomach of Mongolian gerbils (Meriones unguiculatus). Parasitol. Res., 102(4): 587–595. DOI: 10.1007/s00436-007-0792-4 http://dx.doi.org/10.1007/s00436-007-0792-4

[19] Lee, D. L. (1996): Why do some nematode parasites of the alimentary tract secrete acetylcholinesterase? Int. J. Parasitol., 26(5): 499–508 http://dx.doi.org/10.1016/0020-7519(96)00040-9

[20] Mallet, S., Hoste, H. (1995): Physiology of two strains of Trichostrongylus colubriformis resistant and susceptible to thiabendazole and mucosal response of experimentally infected rabbits. Int. J. Parasitol., 25(1): 23–27. DOI: 10.1016/0020-7519(94)00080-8 http://dx.doi.org/10.1016/0020-7519(94)00080-8

[21] Miller, H. R. P. (1984): The protective mucosal response against gastrointestinal nematodes in ruminants and laboratory animals. Vet. Immunol. Immunopathol., 6(1–2): 167–259 http://dx.doi.org/10.1016/0165-2427(84)90051-5

[22] Miller, H. R. P. (1987): Gastrointestinal mucus, a medium for survival and for elimination of parasitic nematodes and protozoa. Parasitology, 94(S1): S77–S100. DOI: 10.1017/S0031182000085838 http://dx.doi.org/10.1017/S0031182000085838

[23] Meeusen, E. N. T., Balic, A. (2000): Do eosinophils have a role in killing helminth parasite? Parasitol. Today, 16 3): 95–101 http://dx.doi.org/10.1016/S0169-4758(99)01607-5

[24] Mezey, E., Palkovits, M. (1992): Localization of targets for anti-ulcer drugs in cells of the immune system. Science, 4, 258 (5088): 1662–1665. DOI: 10.1126/science.1333642 http://dx.doi.org/10.1126/science.1333642

[25] Molento, M. B., Prichard, R. K. (1999): Effects of the multidrug-resistance-reversing agents verapamil and CL 347,099 on the efficacy of ivermectin or moxidectin against unselected and drug-selected strains of Haemonchus contortus in jirds (Meriones unguiculatus). Parasitol. Res., 85(12): 1007–1011 http://dx.doi.org/10.1007/s004360050673

[26] Nassauw, L. V., Adriaensen, D., Timmermans, J. P. 2007): The bidirectional communication between neurons and mast cells within the gastrointestinal tract. Autonomic Neuroscience: Basic and Clinical, 133: 91–103. DOI: 10.1016/j.autneu.2006.10.003 http://dx.doi.org/10.1016/j.autneu.2006.10.003

[27] Ostlind, D. A., Cifelli, S., Mickle, W. G., Smith, S. K., Ewanciw, D. V., Rafalko, B., Felcetto, T., Misura, A. 2006): Evaluation of broad-spectrum anthelmintic activity in a novel assay against Haemonchus contortus, Trichostrongylus colubriformis and T. sigmodontis in the gerbil Meriones unguiculatus. J. Helminthol., 80(4): 393–396. DOI: 10.1017/JOH2006371 http://dx.doi.org/10.1017/JOH2006371

[28] Rojas, D. K., López, J., Tejada, I., Vázquez, V., Shimada, A., Sánchez, D., Ibarra, F. (2006): Impact of condensed tannins from tropical forages on Haemonchus contortus burdens in Mongolian gerbils (Meriones unguiculatus) and Pelibuey lambs. Animal Feed Science and Technology, 128(3 - 4): 218–228. DOI: 10.1016/j.anifeedsci.2005.10.008 http://dx.doi.org/10.1016/j.anifeedsci.2005.10.008

[29] Roos, M. H., Otsen, M., Hoekstra, R., Veenstra, J. G., Lenstra, J. A. (2004): Genetic analysis of inbreeding of two strains of the parasitic nematode Haemonchus contortus. Int. J. Parasitol., 34(1): 109–115. DOI: 10.1016/j.ijpara.2003.10.002 http://dx.doi.org/10.1016/j.ijpara.2003.10.002

[30] Samson-Himmelstjerna, G., Coles, G. C., Jackson, F., Bauer, Ch., Borgsteede, F., Cirak, V., Demeler, J., Donnan, A., Dorny, P., Epe, Ch., Harder, A., Hoglund, J., Kaminsky, R., Kerboeuf, D., Kuettler, U., Papadopoulos, E., Posedi, J., Small, J., VÁRADY, M., Vercruysse, J., Wirtherle, N. (2009): Standardization of the egg hatch test for the detection of benzimidazole resistance in parasitic nematodes. Parasitol. Res., 105(3): 825–834. DOI: 10.1007/s00436-009-1466-1 http://dx.doi.org/10.1007/s00436-009-1466-1

[31] Sellge, G., Lorentz, A., Gebhardt, T., Levi-Schaffer, F., Bektas, H., Manns, M. P., Schuppan, D., Bischoff, S. C. (2004): Human intestinal fibroblasts prevent apoptosis in human intestinal mast cells by a mechanism independent of stem cell factor, IL-3, IL-4, and nerve growth factor. J. Immunol., 172(1): 260–267

[32] Sutherland, I. A., Lee, D. L. (1993): Acetylcholinesterase in infective-stage larvae of Haemonchus contortus, Ostertagia circumcincta and Trichostrongylus colubriformis resistant and susceptible to benzimidazole anthelmintics. Parasitology, 107(5): 553–557. DOI: 10.1017/S003118200006813X http://dx.doi.org/10.1017/S003118200006813X

[33] Stear, M. J., Bishop, S. C., Doligalska, M., Duncan J. L., Holmes, P. H., Irvine, J., Mccririe, L., Mackellar, A., Sainski, E., Murray, M. (1995): Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta. Parasitol. Immunol., 17(12): 643–652. DOI: 10.1111/j.1365-3024.1995.tb01010.x http://dx.doi.org/10.1111/j.1365-3024.1995.tb01010.x

[34] Squires, J. M., Foster, J. G., Lindsay, D. S., Caudell, D. L., Zajac, A. M. (2010): Efficacy of an orange oil emulsion as an anthelmintic against Haemonchus contortus in gerbils Meriones unguiculatus) and in sheep. Vet. Parasitol., 172(1–2): 95–99. DOI: 10.1016/j.vetpar.2010.04.017 http://dx.doi.org/10.1016/j.vetpar.2010.04.017

[35] Squires, J. M., Ferreir, j. F. S., Lindsay, D. S., Zajac, A. M. (2011): Effects of artemisinin and Artemisia extracts on Haemonchus contortus in gerbils (Meriones unguiculatus). Vet. Parasitol., 175(1–2): 103–108. DOI: 10.1016/j.vetpar.2010.09.011 http://dx.doi.org/10.1016/j.vetpar.2010.09.011

[36] Tsubokawa, D., Goso, Y., Nakamura, T., Maruyama, H., Yatabe, F., Kurihara, M., Ichikawa, T., Ishihara, K. (2012): Rapid and specific alteration of goblet cell mucin in rat airway and small intestine associated with resistance against Nippostrongylus brasiliensis reinfection. Experimental Parasitology, 130(3): 209–217. DOI: 10.1016/j.exppara.2012.01.002 http://dx.doi.org/10.1016/j.exppara.2012.01.002

[37] Várady, M., Papadopoulos, E., Dolinská, M., Königová, A. (2011): Anthelmintic resistance in parasites of small ruminants: sheep versus goats. Helminthologia, 48(3): 137–144. DOI: 10.2478/s11687-011-0021-7 http://dx.doi.org/10.2478/s11687-011-0021-7

[38] Watanabe, N., Nawa, Y., Okamoto, K., Kobayashi, A. 1994): Expulsion of Hymenolepis nana from mice with congenital deficiencies of IgE production or mast cell development. Parasite Immunol., 16(3): 137–144. DOI: 10.1111/j.1365-3024.1994.tb00333.x http://dx.doi.org/10.1111/j.1365-3024.1994.tb00333.x

[39] Winter, B. Y., van Den Wijngaard, R. M., De Jonge, W. J. (2012): Intestinal mast cells in gut inflammation and motility disturbances. Biochim. Biophys. Acta, 1822: 66–73. DOI: 10.1016/j.bbadis.2011.03.016 http://dx.doi.org/10.1016/j.bbadis.2011.03.016

[40] White, W. H., Gutierrez, J. A., Naylor, S. A., Cook, C. A., Gonzalez, I. C., Wisehart, M. A., Smith, Ch. K., Thompson, W. A. (2007): In vitro and in vivo characterization of p-amino-phenethyl-m-trifluoromethylphenyl piperazine (PAPP), a novel serotonergic agonist with anthelmintic activity against Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis. Vet. Parasitol., 146(1–2): 58–65. DOI: 10.1016/j.vetpar. 2007.02.014 http://dx.doi.org/10.1016/j.vetpar.2007.02.014

[41] Zurier, R. B., Weissmann, G., Hoffstein, S., Kammerman, S., Tai, H. H. (1974): Mechanisms of lysosomal enzyme release from human leukocytes II. Effects of cAMP and cGMP, autonomic agonists, and agents which affect microtubule function. Clin. Invest., 53(1): 297–309. DOI: 10.1172/JCI107550 http://dx.doi.org/10.1172/JCI107550

Journal Information


IMPACT FACTOR 2017: 0.417
5-year IMPACT FACTOR: 0.619

CiteScore 2016: 0.58

SCImago Journal Rank (SJR) 2015: 0.316
Source Normalized Impact per Paper (SNIP) 2015: 0.678

Target Group researchers in the field of human, veterinary medicine and natural science

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 156 156 16
PDF Downloads 39 39 9