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Migration of Fasciola hepatica newly excysted juveniles is inhibited by high-mannose and oligomannose-type N-glycan-binding lectins

  • ANDRES GARCIA-CAMPOS (a1) (a2), ALAN W. BAIRD (a1) (a2) and GRACE MULCAHY (a1) (a2)


Fasciola hepatica has both zoonotic importance and high economic impact in livestock worldwide. After ingestion by the definitive host, the Newly Excysted Juveniles (NEJ) penetrate the intestine before reaching the peritoneal cavity. The role of some NEJ-derived proteins in invasion has been documented, but the role of NEJ glycans or lectin-binding receptors during initial infection in the gut is still unknown. To address these questions, the migration of NEJ through rat intestine was recorded at 30 min intervals up to 150 min by two ex vivo methods. Firstly, jejunal sheets were challenged with NEJ incubated with biotinylated lectins. Secondly, untreated NEJ were incubated with distal jejunum pre-treated with lectins. Both Concanavalin A (ConA) and Galanthus nivalis (GNL), which recognize mannose-type N-glycans, significantly inhibited NEJ migration across the jejunum. Most of the lectins bound to the tegument and oral sucker of the NEJ, but only ConA and GNL maintained this interaction over 150 min. None of the lectins examined significantly reduced NEJ migration when pre-incubated with jejunal sheets, suggesting that host glycans might not be essential for initial binding/recognition of the gut by NEJ. Agents capable of blocking mannose-type N-glycans on the NEJ tegument may have potential for disrupting infection.


Corresponding author

*Corresponding author: School of Veterinary Medicine, University College Dublin, Veterinary Sciences Centre, Belfield, Dublin 4, Ireland. E-mail:


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Astronomo, R. D. and Burton, D. R. (2010). Carbohydrate vaccines: developing sweet solutions to sticky situations? Nature Reviews. Drug Discovery 9, 308324.
Barbosa, H. S. and de Meirelles, M. de N. (1992). Ultrastructural detection in vitro of WGA-, RCA I-, and Con A-binding sites involved in the invasion of heart muscle cells by Trypanosoma cruzi . Parasitology Research 78, 404409.
Barnes, D. A., Bonnin, A., Huang, J. X., Gousset, L., Wu, J., Gut, J., Doyle, P., Dubremetz, J. F., Ward, H. and Petersen, C. (1998). A novel multi-domain mucin-like glycoprotein of Cryptosporidium parvum mediates invasion. Molecular and Biochemical Parasitology 96, 93110.
Barondes, S. H., Cooper, D. N., Gitt, M. A. and Leffler, H. (1994). Galectins. Structure and function of a large family of animal lectins. Journal of Biological Chemistry 269, 2080720810.
Brzezicka, K., Echeverria, B., Serna, S., van Diepen, A., Hokke, C. H. and Reichardt, N.-C. (2015). Synthesis and microarray-assisted binding studies of core xylose and fucose containing N-glycans. ACS Chemical Biology 10, 12901302.
Caffaro, C. E., Koshy, A. A., Liu, L., Zeiner, G. M., Hirschberg, C. B. and Boothroyd, J. C. (2013). A nucleotide sugar transporter involved in glycosylation of the Toxoplasma tissue cyst wall is required for efficient persistence of bradyzoites. PLoS Pathogens 9, e1003331.
Cancela, M., Ruétalo, N., Dell'Oca, N., da Silva, E., Smircich, P., Rinaldi, G., Roche, L., Carmona, C., Alvarez-Valín, F., Zaha, A. and Tort, J. F. (2010). Survey of transcripts expressed by the invasive juvenile stage of the liver fluke Fasciola hepatica . BMC Genomics 11, 227.
Cancela, M., Santos, G. B., Carmona, C., Ferreira, H. B., Tort, J. F. and Zaha, A. (2015). Fasciola hepatica mucin-encoding gene: expression, variability and its potential relevance in host-parasite relationship. Parasitology 142, 16731681.
Carmona, C., Dowd, A. J., Smith, A. M. and Dalton, J. P. (1993). Cathepsin L proteinase secreted by Fasciola hepatica in vitro prevents antibody-mediated eosinophil attachment to newly excysted juveniles. Molecular and Biochemical Parasitology 62, 917.
Cevallos, A. M., Bhat, N., Verdon, R., Hamer, D. H., Stein, B., Tzipori, S., Pereira, M. E., Keusch, G. T. and Ward, H. D. (2000). Mediation of Cryptosporidium parvum infection in vitro by mucin-like glycoproteins defined by a neutralizing monoclonal antibody. Infection and Immunity 68, 51675175.
Chadee, K., Petri, W. A., Innes, D. J. and Ravdin, J. I. (1987). Rat and human colonic mucins bind to and inhibit adherence lectin of Entamoeba histolytica . Journal of Clinical Investigation 80, 12451254.
Charyasriwong, S., Haruyama, T. and Kobayashi, N. (2016). In vitro evaluation of the antiviral activity of methylglyoxal against influenza B virus infection. Drug Discoveries and Therapeutics 10, 201210.
Chen, X.-M. M. and LaRusso, N. F. (2000). Mechanisms of attachment and internalization of Cryptosporidium parvum to biliary and intestinal epithelial cells. Gastroenterology 118, 368379.
Choudhry, N., Bajaj-Elliott, M. and McDonald, V. (2008). The terminal sialic acid of glycoconjugates on the surface of intestinal epithelial cells activates excystation of Cryptosporidium parvum . Infection and Immunity 76, 37353741.
Cwiklinski, K., Dalton, J. P., Dufresne, P. J., La Course, J., Williams, D. J. L., Hodgkinson, J. and Paterson, S. (2015). The Fasciola hepatica genome: gene duplication and polymorphism reveals adaptation to the host environment and the capacity for rapid evolution. Genome Biology 16, 71.
Cwiklinski, K., O'Neill, S. M., Donnelly, S. and Dalton, J. P. (2016). A prospective view of animal and human Fasciolosis. Parasite Immunology 38, 558568.
Dalle, F., Jouault, T., Trinel, P. A., Esnault, J., Mallet, J. M., D'Athis, P., Poulain, D. and Bonnin, A. (2003). Beta-1,2- and alpha-1,2-linked oligomannosides mediate adherence of Candida albicans blastospores to human enterocytes in vitro . Infection and Immunity 71, 70617068.
Dalton, J. P. and Joyce, P. (1987). Characterization of surface glycoproteins and proteins of different developmental stages of Fasciola hepatica by surface radiolabeling. Journal of Parasitology 73, 12811284.
Dromer, F., Chevalier, R., Sendid, B., Improvisi, L., Jouault, T., Robert, R., Mallet, J. M. and Poulain, D. (2002). Synthetic analogues of beta-1,2 oligomannosides prevent intestinal colonization by the pathogenic yeast Candida albicans . Antimicrobial Agents and Chemotherapy 46, 38693876.
Fradin, C., Poulain, D. and Jouault, T. (2000). β−1,2-linked oligomannosides from Candida albicans bind to a 32-kilodalton macrophage membrane protein homologous to the mammalian lectin galectin-3. Infection and Immunity 68, 43914398.
Garcia-Campos, A., Baird, A. W. and Mulcahy, G. (2016 a). Development of a versatile in vitro method for understanding the migration of Fasciola hepatica newly excysted juveniles. Parasitology 143, 2433.
Garcia-Campos, A., Ravidà, A., Nguyen, D. L., Cwiklinski, K., Dalton, J. P., Hokke, C. H., O'Neill, S. and Mulcahy, G. (2016 b). Tegument glycoproteins and cathepsins of newly excysted juvenile Fasciola hepatica carry mannosidic and paucimannosidic n-glycans. PLoS Neglected Tropical Diseases 10, e0004688.
Hanna, R. (1980). Fasciola hepatica: autoradiography of protein synthesis, transport, and secretion by the tegument. Experimental Parasitology 50, 297304.
Hashim, A., Mulcahy, G., Bourke, B. and Clyne, M. (2006). Interaction of Cryptosporidium hominis and Cryptosporidium parvum with primary human and bovine intestinal cells. Infection and Immunity 74, 99107.
Hulley, S., Cummings, S., Browner, W., Grady, D. and Newman, T. (2013). Designing clinical research: an epidemiologic approach. In Designing Clinical Research: an Epidemiologic Approach Lippincott Williams & Wilkins, Philadelphia, p. 73.
Inge, P. M., Edson, C. M. and Farthing, M. J. (1988). Attachment of Giardia lamblia to rat intestinal epithelial cells. Gut 29, 795801.
Irwin, J. A., Morrissey, P. E. W., Ryan, J. P., Walshe, A., O'Neill, S. M., Carrington, S. D., Matthews, E., Fitzpatrick, E., Mulcahy, G., Corfield, A. P. and Dalton, J. P. (2004). Glycosidase activity in the excretory-secretory products of the liver fluke, Fasciola hepatica . Parasitology 129, 465472.
Jouault, T., Fradin, C., Trinel, P. A., Bernigaud, A. and Poulain, D. (1998). Early signal transduction induced by Candida albicans in macrophages through shedding of a glycolipid. Journal of Infectious Diseases 178, 792802.
Kania, P. W., Sorensen, R. R., Koch, C., Brandt, J., Kliem, A., Vitved, L., Hansen, S. and Skjodt, K. (2010). Evolutionary conservation of mannan-binding lectin (MBL) in bony fish: identification, characterization and expression analysis of three bona fide collectin homologues of MBL in the rainbow trout (Onchorhynchus mykiss). Fish and Shellfish Immunology 29, 910920.
Kawano, J., Yamamoto, T., Koga, M., Shimizu, A. and Kimura, S. (1991). Penetration in vitro of newly excysted juvenile flukes of Japanese Fasciola sp. through ligated intestines of rabbits, mice, rats and chickens. Journal of Veterinary Medicine Science 54, 6973.
Lammas, D., Duffus, W. and Taylor, D. (1985). Identification of surface proteins of juvenile stages of Fasciola hepatica . Research in Veterinary Sciences 38, 248249.
McGonigle, L., Mousley, A., Marks, N. J., Brennan, G. P., Dalton, J. P., Spithill, T. W., Day, T. A. and Maule, A. G. (2008). The silencing of cysteine proteases in Fasciola hepatica newly excysted juveniles using RNA interference reduces gut penetration. International Journal for Parasitology 38, 149155.
McVay, C. S., Bracken, P., Gagliardo, L. F. and Appleton, J. (2000). Antibodies to tyvelose exhibit multiple modes of interference with the epithelial niche of Trichinella spiralis . Infection and Immunity 68, 19121918.
Moore, M. N. and Halton, D. W. (1976). Fasciola hepatica: histochemical observations on juveniles and adults and the cytopathological changes induced in infected mouse liver. Experimental Parasitology 40, 212224.
Nair, M. G., Guild, K. J. and Artis, D. (2006). Novel effector molecules in type 2 inflammation: lessons drawn from helminth infection and allergy. Journal of Immunology 177, 13931399.
Petropolis, D. B., Faust, D. M., Deep Jhingan, G. and Guillen, N. (2014). A new human 3D-liver model unravels the role of galectins in liver infection by the parasite Entamoeba histolytica . PLoS Pathogens 10, e1004381.
Preston, S. J. M., Beddoe, T., Walkden-Brown, S., Meeusen, E. and Piedrafita, D. (2015). Galectin-11: a novel host mediator targeting specific stages of the gastrointestinal nematode parasite, Haemonchus contortus . International Journal for Parasitology 45, 791796.
Redondo, M. J. and Alvarez-Pellitero, P. (2010). The effect of lectins on the attachment and invasion of Enteromyxum scophthalmi (Myxozoa) in turbot (Psetta maxima L.) intestinal epithelium in vitro . Experimental Parasitology 126, 577581.
Ríos-de Álvarez, L., Jackson, F., Greer, A., Bartley, Y., Bartley, D. J., Grant, G. and Huntley, J. F. (2012). In vitro screening of plant lectins and tropical plant extracts for anthelmintic properties. Veterinary Parasitology 186, 390398.
Robinson, M. W., Menon, R., Donnelly, S. M., Dalton, J. P. and Ranganathan, S. (2009). An integrated transcriptomics and proteomics analysis of the secretome of the helminth pathogen Fasciola hepatica: proteins associated with invasion and infection of the mammalian host. Molecular and Cellular Proteomics: MCP 8, 18911907.
Robinson, M. W., Hutchinson, A. T., Donnelly, S. and Dalton, J. P. (2010). Worm secretory molecules are causing alarm. Trends in Parasitology 26, 371372.
Santos, I. K., Costa, C. H., Krieger, H., Feitosa, M. F., Zurakowski, D., Fardin, B., Gomes, R. B., Weiner, D. L., Harn, D. A., Ezekowitz, R. A. and Epstein, J. (2001). Mannan-binding lectin enhances susceptibility to visceral leishmaniasis. Infection and Immunity 69, 52125215.
Sousa, M. C., Gonçalves, C. A., Bairos, V. A. and Poiares-Da-Silva, J. (2001). Adherence of Giardia lamblia trophozoites to Int-407 human intestinal cells. Clinical and Diagnostic Laboratory Immunology 8, 258265.
Uemura, K., Saka, M., Nakagawa, T., Kawasaki, N., Thiel, S., Jensenius, J. C. and Kawasaki, T. (2002). L-MBP is expressed in epithelial cells of mouse small intestine. Journal of Immunology 169, 69456950.
Weis, W. I., Drickamer, K. and Hendrickson, W. A. (1992). Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature 360, 127134.
Wrackmeyer, U., Hansen, G. H., Seya, T. and Danielsen, E. M. (2006). Intelectin: a novel lipid raft-associated protein in the enterocyte brush border. Biochemistry 45, 91889197.
Zuo, D.-M., Zhang, L.-Y., Lu, X., Liu, Y. and Chen, Z.-L. (2009). Protective role of mouse MBL-C on intestinal mucosa during Shigella flexneri invasion. International Immunology 21, 11251134.
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