The Innate Immunity Defense against Gastrointestinal Nematodes: Vaccine Development

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Narges Lotfalizadeh
Soheil Sadr
Safa Moghaddam
Mahdis Saberi Najjar
Amin Khakshoor
Pouria Ahmadi Simab


The nematode parasite infects both humans and animals, causing severe infections. Their unusual surface structures, in particular, pose significant challenges to the immune system. Vaccine-induced immunity, mediated by the innate immune system, could be crucial in the development of an adaptive effector response. The purpose of this paper was to provide an overview of recent research on the host's innate immune system, barriers, and cells that respond to parasitic nematodes. This study investigated the nematode-associated molecular patterns that may recognize by host. Given the innate defense is more than just a static barrier against pathogen infections. It can actively contribute as a director of the adaptive immune response, which is ultimately responsible for the rejection of invasions. The role of innate defense against pathogen infections is located in zone of researcher concentration. Some nematode parasites can actively move through tissues, they pose a challenge to the innate immune system. Furthermore, their cuticular surface, which varies with each molting, cannot be phagocytosed. The nematode's thin, carbohydrate-rich surface layer, as well as the chemicals produced by this layer, cause the first contact with the host's innate immune system. Notably, all components of the innate immune response can be activated and play an important role in the adaptive immune effector response.

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Lotfalizadeh, N., Sadr, S., Moghaddam, S., Saberi Najjar, M., Khakshoor, A., & Ahmadi Simab, P. (2022). The Innate Immunity Defense against Gastrointestinal Nematodes: Vaccine Development. Farm Animal Health and Nutrition, 1(2), 31–38.
Review Article


Sorobetea D, Svensson-Frej M, and Grencis R. Immunity to gastrointestinal nematode infections. Mucosal Immunol. 2018; 11(2): 304-315. DOI:

Stepek G, Buttle DJ, Duce IR, and Behnke JM. Human gastrointestinal

nematode infections: Are new control methods required?. Int J Exp Pathol. 2006; 87(5): 325-341. DOI: 2613.2006.00495.x

Veesenmeyer AF. Important nematodes in children. Pediatr Clin North Am. 2022; 69(1): 129-139. DOI:

Charlier J, Höglund J, Morgan ER, Geldhof P, Vercruysse J, and Claerebout E. Biology and epidemiology of gastrointestinal nematodes in cattle. Vet Clin North Am Food Anim Pract. 2020; 36(1): 1-15. DOI:

Charlier J, Thamsborg SM, Bartley DJ, Skuce PJ, Kenyon F, Geurden T, et al. Mind the gaps in research on the control of gastrointestinal nematodes of farmed ruminants and pigs. Transbound Emerg Dis. 2018; 65(Suppl 1): 217-234. DOI:

Vercruysse J, Charlier J, Van Dijk J, Morgan ER, Geary T, von Samson- Himmelstjerna G, et al. Control of helminth ruminant infections by 2030. Parasitology. 2018; 145(13): 1655-1664. DOI:

Cortés A, Rooney J, Bartley DJ, Nisbet AJ, and Cantacessi C. Helminths, hosts, and their microbiota: new avenues for managing gastrointestinal helminthiases in ruminants. Expert Rev Anti Infect Ther. 2020; 18(10): 977-985. DOI: 14787210.2020.1782188

Emery DL, Hunt PW, and Le Jambre LF. Haemonchus contortus: The then and now, and where to from here?. Int J Parasitol. 2016; 46(12): 755-769. DOI:

Miller JE, and Horohov DW. Immunological aspects of nematode parasite control in sheep. J Anim Sci. 2006; 84(Suppl-13): E124-E132. DOI:

Biffa D, Jobre Y, and Chakka H. Ovine helminthosis, a major health constraint to productivity of sheep in Ethiopia. Anim Health Res Rev. 2006; 7(1-2): 107-118. DOI: 7001132

Sharpe C, Thornton DJ, and Grencis RK. A sticky end for gastrointestinal helminths: The role of the mucus barrier. Parasite Immunol. 2018; 40(4): e12517. DOI:

Grondin JA, Kwon YH, Far PM, Haq S, and Khan WI. Mucins in intestinal mucosal defense and inflammation: Learning from clinical and experimental studies. Front Immunol. 2020; 4(11): 2054. DOI:

Van den Abbeele P, Van de Wiele T, Verstraete W, and Possemiers S. The host selects mucosal and luminal associations of coevolved gut microorganisms: A novel concept. FEMS Microbiol Rev. 2011; 35(4): 681-704. DOI: 00270.x

McRae KM, Stear MJ, Good B, and Keane OM. The host immune response to gastrointestinal nematode infection in sheep. Parasite Immunol. 2015; 37(12): 605-613. DOI:

Artis D, and Grencis RK. The intestinal epithelium: Sensors to effectors in nematode infection. Mucosal Immunol. 2008; 1(4): 252-264. DOI:

Kyngdon CT, Gauci CG, Rolfe RA, Velásquez Guzmán JC, Farfán Salazar MJ, Verástegui Pimentel MR, et al. In vitro oncosphere-killing assays to determine immunity to the larvae of Taenia pisiformis, Taenia ovis, Taenia saginata, and Taenia solium. J Parasitol. 2006; 92(2): 273-281. DOI:

Harrison E, Lal S, and McLaughlin JT. Enteroendocrine cells in gastrointestinal pathophysiology. Curr Opin Pharmacol. 2013; 13(6): 941-945. DOI:

Luzio JP, Pryor PR, and Bright NA. Lysosomes: Fusion and function. Nat Rev Mol Cell Biol. 2007; 8(8): 622-632. DOI:

Winterbourn CC, Kettle AJ, and Hampton MB. Reactive oxygen species and neutrophil function. Annu Rev Biochem. 2016; 2(85): 765-792. DOI:

Langrish CL, McKenzie BS, Wilson NJ, de Waal Malefyt R, Kastelein RA, and Cua DJ. IL-12 and IL-23: Master regulators of innate and adaptive immunity. Immunol Rev. 2004; 202: 96-105. DOI:

Viola MF, and Boeckxstaens G. Intestinal resident macrophages: Multitaskers of the gut. Neurogastroenterol Motil. 2020; 32(8): e13843. DOI:

Maizels RM, Balic A, Gomez-Escobar N, Nair M, Taylor MD, and Allen JE. Helminth parasites--masters of regulation. Immunol Rev. 2004; 201: 89-116. DOI:

Hodžić A, Mateos-Hernández L, Fréalle E, Román-Carrasco P, Alberdi P, Pichavant M, et al. Infection with Toxocara canis inhibits the

production of IgE antibodies to α-Gal in humans: Towards a conceptual framework of the hygiene hypothesis? Vaccines (Basel). 2020; 8(2): 167. DOI:

Gruden-Movsesijan A, and Milosavljevic LjS. The involvement of the macrophage mannose receptor in the innate immune response to infection with parasite Trichinella spiralis. Vet Immunol Immunopathol. 2006; 109(1-2): 57-67. DOI:

Cooper D, and Eleftherianos I. Parasitic nematode immunomodulatory strategies: Recent advances and perspectives. Pathogens. 2016; 5(3): 58. DOI:

Jenkins SJ, and Allen JE. Similarity and diversity in macrophage activation by nematodes, trematodes, and cestodes. J Biomed Biotechnol. 2010; 2010: 262609. DOI:

Whelan M, Harnett MM, Houston KM, Patel V, Harnett W, and Rigley KP. A filarial nematode-secreted product signals dendritic cells to acquire a phenotype that drives development of Th2 cells. J Immunol. 2000; 164(12): 6453-6460. DOI: 164.12.6453

Motran CC, Silvane L, Chiapello LS, Theumer MG, Ambrosio LF, Volpini X, et al. Helminth infections: Recognition and modulation of the immune response by innate immune cells. Front Immunol. 2018; 4(9): 664. DOI:

Segura M, Su Z, Piccirillo C, and Stevenson MM. Impairment of dendritic cell function by excretory-secretory products: A potential mechanism for nematode-induced immunosuppression. Eur J Immunol. 2007; 37(7): 1887-1904. DOI:

Maruyama H, Yabu Y, Yoshida A, Nawa Y, and Ohta N. A role of mast cell glycosaminoglycans for the immunological expulsion of intestinal nematode, Strongyloides Venezuelensis. J Immunol. 2000; 164(7): 3749-354. DOI:

McDermott JR, Bartram RE, Knight PA, Miller HRP, Garrod DR, and Grencis RK. Mast cells disrupt epithelial barrier function during enteric nematode infection. Proc Natl Acad Sci USA. 2003; 100(13): 7761-7766. DOI:

Obata-Ninomiya K, Domeier PP, and Ziegler SF. Basophils and eosinophils in nematode infections. Front Immunol. 2020; 27(11): 583824. DOI:

Huang L, Gebreselassie NG, Gagliardo LF, Ruyechan MC, Luber KL, Lee NA, et al. Eosinophils mediate protective immunity against secondary nematode infection. J Immunol. 2015; 194(1): 283-290. DOI:

Gebreselassie NG, Moorhead AR, Fabre V, Gagliardo LF, Lee NA, Lee JJ, et al. Eosinophils preserve parasitic nematode larvae by regulating local immunity. J Immunol. 2012; 188(1): 417-425. DOI:

Ravin KA, and Loy M. The eosinophil in infection. Clin Rev Allergy Immunol. 2016; 50(2): 214-227. DOI:

Lin A, and Loré K. Granulocytes: New members of the antigen- presenting cell family. Front Immunol. 2017; 11(8): 1781. DOI:

Padigel UM, Hess JA, Lee JJ, Lok JB, Nolan TJ, Schad GA, et al. Eosinophil’s act as antigen-presenting cells to induce immunity to Strongyloides stercoralis in mice. J Infect Dis. 2007; 196(12): 1844- 1851. DOI:

Bhogal HS. Characterization of galectins in the sheep ileal Peyer’s patch (Unpublished Doctoral Thesis). University of Calgary, Calgary, Canada. 2002. DOI:

Grozdanovic MM, Doyle CB, Liu L, Maybruck BT, Kwatia MA, Thiyagarajan N, et al. Charcot-Leyden crystal protein/galectin-10 interacts with cationic ribonucleases and is required for eosinophil granulogenesis. J Allergy Clin Immunol. 2020; 146(2): 377-389.e10. DOI:

Acharya KR, and Ackerman SJ. Eosinophil granule proteins: Form and function. J Biol Chem. 2014; 289(25): 17406-17415. DOI:

Rothenberg ME, and Hogan SP. The eosinophil. Annu Rev Immunol. 2006; 24: 147-174. DOI: 24.021605.090720

Gigon L, Yousefi S, Karaulov A, and Simon HU. Mechanisms of toxicity mediated by neutrophil and eosinophil granule proteins. Allergol Int. 2021; 70(1): 30-38. DOI:

Meza Guzman LG, Keating N, and Nicholson SE. Natural killer cells: Tumor surveillance and signaling. Cancers(Basel). 2020; 12(4): 952. DOI:

Shokal U, and Eleftherianos I. Evolution and function of thioester- containing proteins and the complement system in the innate immune response. Front Immunol. 2017; (29)8: 759. DOI:

Turner CE. Paxillin and focal adhesion signalling. Nat Cell Biol. 2000; 2(12): E231-E236. DOI:

Gros P, Milder FJ, and Janssen BJ. Complement driven by conformational changes. Nat Rev Immunol. 2008; 8(1): 48-58. DOI:

Zhang Z, Yang J, Wei J, Yang Y, Chen X, Zhao X, et al. Trichinella spiralis paramyosin binds to C8 and C9 and protects the tissue- dwelling nematode from being attacked by host complement. PLoS Negl Trop Dis. 2011; 5(7): e1225. DOI:

Colditz IG. Six costs of immunity to gastrointestinal nematode infections. Parasite Immunol. 2008; 30(2): 63-70. DOI: 00964.x

Brennan JJ, and Gilmore TD. Evolutionary origins of toll-like receptor signaling. Mol Biol Evol. 2018; 35(7): 1576-1587. DOI:

Irazoqui JE, Urbach JM, and Ausubel FM. Evolution of host innate defence: Insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol. 2010; 10(1): 47-58. DOI:

Maizels RM, and McSorley HJ. Regulation of the host immune system by helminth parasites. J Allergy Clin Immunol. 2016; 138(3): 666-675. DOI:

Prasanphanich NS, Mickum ML, Heimburg-Molinaro J, and Cummings RD. Glycoconjugates in host-helminth interactions. Front Immunol. 2013; 28(4): 240. DOI:

Bashi T, Bizzaro G, Ben-Ami SD, Blank M, and Shoenfeld Y. The mechanisms behind helminth’s immunomodulation in autoimmunity. Autoimmun Rev. 2015; 14(2): 98-104. DOI: autrev.2014.10.004

Bobardt SD, Dillman AR, and Nair MG. The two faces of nematode infection: Virulence and immunomodulatory molecules from nematode parasites of mammals, insects and plants. Front Microbiol. 2020; 2(11): 577846. DOI:

Kahl J, Brattig N, and Liebau E. The untapped pharmacopeic potential of helminths. Trends Parasitol. 2018; 34(10): 828-842. DOI:

Wilbers RHP, Schneiter R, Holterman MHM, Drurey C, Smant G, Asojo OA, et al. Secreted venom allergen-like proteins of helminths: Conserved modulators of host responses in animals and plants. PLoS Pathog. 2018; 14(10): e1007300. DOI:

Luo L, Kamau PM, and Lai R. Bioactive peptides and proteins from wasp venoms. Biomolecules. 2022; 12(4): 527. DOI:

Lee SH, Baek JH, and Yoon KA. Differential properties of venom peptides and proteins in solitary vs. social hunting wasps. Toxins (Basel). 2016; 8(2): 32. DOI:

Maruszewska-Cheruiyot M, Szewczak L, Krawczak-Wójcik K, Głaczyńska M, and Donskow-Łysoniewska K. The production of excretory-secretory molecules from Heligmosomoides polygyrus bakeri fourth stage larvae varies between mixed and single sex cultures. Parasit Vectors. 2021; 14(1): 106. DOI:

Stoltzfus JD, Pilgrim AA, and Herbert DR. Perusal of parasitic nematode omics in the post-genomic era. Mol Biochem Parasitol. 2017; 215: 11-22. DOI:

Reynolds LA, Filbey KJ, and Maizels RM. Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus. Semin Immunopathol. 2012; 34(6): 829-846. DOI:

Britton C, Emery DL, McNeilly TN, Nisbet AJ, and Stear MJ. The potential for vaccines against scour worms of small ruminants. Int J Parasitol. 2020; 50(8): 533-553. DOI:

Molehin AJ, Gobert GN, and McManus DP. Serine protease inhibitors of parasitic helminths. Parasitology. 2012; 139(6): 681-695. DOI:

Ranasinghe S, and McManus DP. Structure and function of invertebrate Kunitz serine protease inhibitors. Dev Comp Immunol. 2013; 39(3): 219-227. DOI:

Zamanian M, Fraser LM, Agbedanu PN, Harischandra H, Moorhead AR, Day TA, et al. Release of small RNA-containing exosome-like vesicles

from the human filarial parasite Brugia Malaya. PLoS Negl Trop Dis. 2015; 9(9): e0004069. DOI:

Babu S, and Nutman TB. Immunology of lymphatic filariasis. Parasite Immunol. 2014; 36(8): 338-346. DOI:

Nisbet AJ, Meeusen EN, González JF, and Piedrafita DM. Immunity to Haemanthus contortus and Vaccine development. Adv Parasitol. 2016; 93: 353-396. DOI:

Adduci I, Sajovitz F, Hinney B, Lichtmannsperger K, Joachim A, Wittek T, et al. Haemonchosis in sheep and goats, control strategies and development of vaccines against Haemonchus contortus. Animals (Basel). 2022; 12(18): 2339. DOI:

Stutzer C, Richards SA, Ferreira M, Baron S, and Maritz-Olivier C. Metazoan parasite vaccines: Present status and future prospects. Front Cell Infect Microbiol. 2018; 13(8): 67. DOI:

Claerebout E, and Geldhof P. Helminth vaccines in ruminants: From development to application. Vet Clin North Am Food Anim Pract. 2020; 36(1): 159-171. DOI:

Matthews JB, Geldhof P, Tzelos T, and Claerebout E. Progress in the development of subunit vaccines for gastrointestinal nematodes of ruminants. Parasite Immunol. 2016; 38(12): 744-753. DOI:

Fawzi EM, González-Sánchez ME, Corral MJ, Alunda JM, and Cuquerella M. Vaccination of lambs with the recombinant protein rHc23 elicits significant protection against Haemonchus contortus challenge. Vet Parasitol. 2015; 211(1-2): 54-59. DOI:

Heegaard PM, Dedieu L, Johnson N, Le Potier MF, Mockey M, Mutinelli F, et al. Adjuvants and delivery systems in veterinary vaccinology: Current state and future developments. Arch Virol. 2011; 156(2): 183-202. DOI:

Noon JB, and Aroian RV. Recombinant subunit vaccines for soil- transmitted helminths. Parasitology. 2017; 144(14): 1845-1870. DOI:

Sarkar I, Garg R, and van Drunen Littel-van den Hurk S. Selection of adjuvants for vaccines targeting specific pathogens. Expert Rev Vaccines. 2019; 18(5): 505-521. DOI: 14760584.2019.1604231

Charlier J, Morgan ER, Rinaldi L, van Dijk J, Demeler J, Höglund J, et al. Practices to optimize gastrointestinal nematode control on sheep, goat and cattle farms in Europe using targeted (selective) treatments. Vet Rec. 2014; 175(10): 250-255. DOI:

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