Journal of Parasitic Diseases

, Volume 42, Issue 4, pp 471–482 | Cite as

Immunity to gastrointestinal nematodes in ruminants: effector cell mechanisms and cytokines

  • Seham H. M. HendawyEmail author
Review Article


Gastrointestinal nematodes (GINs) of ruminants are prevalent and have major economic impacts worldwide. The insight studies of immune responses triggered against GINs are of great concern to understand interaction between host’s immune system and parasite. T-helper 2 cytokines drive the effector cell mechanisms which include eosinophils and mast cells. The immune responses are controlled by Th2 secreted interleukins (IL); IL3, IL-4, IL-5, IL-9, IL-10 and IL-13. B-Cell immune response is incorporated in defense mechanisms developed against GINs specially immunoglobulins (Ig); IgA, IgE and IgG. The immune resistance of the infected host is presented by failure of larval establishment or hypobiosis, low worm burden and decreased female fecundity. The host–parasite interaction is a complex series that affected by host’s genetic constitution, nutrition, age and physiological status. The GINs have different immune evasion mechanisms to improve their survival within the host. Also, management of the host influences GINs parasitism. Thus, the aim of this review is to highlight the hallmarks of immune responses that endorse GINs parasitism. The insights studies of the triggered immune responses developed against GINs will improve the appropriate protective immune strategy.


GINs Cytokines MMC Eosinophils Ruminants Evasion 


Compliance with ethical standards

Conflict of interest

The author declares that there is no conflict of interest.

Ethical standards

This review article is prepared and presented by the author in accordance with the ethical standards.


  1. Abdel-Rady A (2014) Epidemiological studies on parasitic infestations in camels (Camelus dromedarius) in Egypt. IJAVMS 8:142–149Google Scholar
  2. Abo-Aziza FAM, Hendawy SHM, El Namaky AH, Ashry HM (2017) Th1/Th2 balance and humoral immune response to potential antigens as early diagnostic method of equine Strongylus nematode infection. Vet World 10:679–687CrossRefGoogle Scholar
  3. Abraham SN, St. John AL (2010) Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol 10:440–452CrossRefGoogle Scholar
  4. Al-Aboody MS, Omar MA (2016) Prevalence of gastrointestinal nematodes of farm animals by copro-culture. Russ J Parasitol 36:168–174Google Scholar
  5. AL-Gaabary MH, Osman SA, Abo EL-Soud KM, Hassan AI (2012) Studies on gastrointestinal nematodes infection in sheep with special reference to Haemonchus contortus. Assiut Vet Med J 58:31–40Google Scholar
  6. Allen JE, Sutherland TE (2014) Host protective roles of type2 immunity: parasite killing and tissue repair flip sides of the same coin. Semin Immunol 26:329–340CrossRefGoogle Scholar
  7. Amarante AFT, Amarante MRV (2016) Advances in the diagnosis of the gastrointestinal nematode infections in ruminants. Braz J Vet Res Anim Sci 53:127–137CrossRefGoogle Scholar
  8. Angulo-Cubillán FJ, García-Coiradas L, Cuquerella M, José CF, Alunda M (2007) Haemonchus contortus-sheep relationship: a review. Rev Cient 17:577–587Google Scholar
  9. Baker RL (1998) A review of genetic resistance to gastrointestinal nematode parasites in sheep and goats in the tropics and evidence for resistance in some sheep and goat breeds in sub-humid coastal Kenya. AGRI 24:13–30Google Scholar
  10. Balic A (1999) Immunobiology of Haemonchus contortus infections in sheep. Ph.D. thesis, University of Melbourne, AustraliaGoogle Scholar
  11. Balic A, Bowles VM, Meeusen EN (2000) The immunobiology of gastrointestinal nematode infections in ruminants. Adv Parasitol 45:181–241CrossRefGoogle Scholar
  12. Balic A, Bowles VM, Meeusen EN (2002) Mechanisms of immunity to Haemonchus contortus infection in sheep. Parasite Immunol 24:39–46CrossRefGoogle Scholar
  13. Balic A, Cunningham CP, Meeusen EN (2006) Eosinophil and nematode interactions with Haemonchus contortus larvae in the ovine gastrointestinal tract. Parasite Immunol 28:107–115CrossRefGoogle Scholar
  14. Barger IA, Siale K, Banks DJD, Le Jambre LF (1994) Rotational grazing for control of gastrointestinal nematodes of goats in a wet tropical environment. Vet Parasitol 53:109–116CrossRefGoogle Scholar
  15. Belina D, Abdurahman G, Mengistu S, Eshetu A (2017) Gastrointestinal nematodes in ruminants: the parasite burden, associated risk factors and anthelmintic utilization practices in selected districts of east and western Hararghe, Ethiopia. J Vet Sci Technol 8:433–440CrossRefGoogle Scholar
  16. Bricarello PA, Amarante AFT, Rocha RA, Cabral Filho SL, Huntley JF, Houdijk JGM, Abdalla AL, Gennari SM (2005) Influence of dietary protein supply on resistance to experimental infection with Haemonchus contortus in Il de France and Santa Ines lambs. Vet Parasitol 134:99–109CrossRefGoogle Scholar
  17. Burke JM, Morrical D, Miller JE (2007) Control of gastrointestinal nematodes with copper oxide wire particles in a flock of lactating Polypay ewes and offspring in Iowa, USA. Vet Parasitol 146:372–375CrossRefGoogle Scholar
  18. Cooper D, Eleftherianos I (2016) Parasitic nematode immunomodulatory strategies: recent advances and perspectives. Pathogens 5:58–70CrossRefGoogle Scholar
  19. Dawicki W, Marshall JS (2007) New and emerging roles for mast cells in host defense. Curr Opin Immunol 19:31–38CrossRefGoogle Scholar
  20. Duque GA, Descoteaux A (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 5:1–12Google Scholar
  21. El Namaky AH, Hendawy SH, Abo-Aziza FA, Ashry HM (2017) Cytokines and immunoglobulin G response in donkeys with spontaneous Setaria equina infection. BJVM. CrossRefGoogle Scholar
  22. Elshahawy IS, Metwally AM, Ibrahim DA (2014) An abattoir-based study on helminthes of slaughtered goats (Capra hircus L., 1758) in Upper Egypt, Egypt. Helminthologia 51:67–72CrossRefGoogle Scholar
  23. Estes DM, Brown WC (2002) Type 1 and type 2 in regulation of Ig isotype expression in cattle. Vet Immunol Immunopathol 90:1–10CrossRefGoogle Scholar
  24. Finkelman FD, Katona IM, Urban JF (1988) IL-4 is required to generate andsustain in vivo IgE responses. J Immunol 141:2335–2341PubMedGoogle Scholar
  25. Frank SA (2002) Immunology and evolution of infectious disease. Princeton University Press, PrincetonGoogle Scholar
  26. Garza JJ (2014) Comparison of immune responses during gastrointestinal helminth self-cure expulsion between resistant Gulf Coast Native and susceptible Suffolk sheep. LSU Doctoral Dissertations, 1019Google Scholar
  27. Gasbarre LC (1997) Effects of gastrointestinal nematode infection on the ruminant immune system. Vet Parasitol 72:327–343CrossRefGoogle Scholar
  28. Gasbarre LC, Leighton EA, Sonstegard T (2001) Role ofthe bovine immune system and genome in resistance to gastrointestinal nematodes. Vet Parasitol 98:51–64CrossRefGoogle Scholar
  29. Gebreselassie NG, Moorhead AR, Fabre V, Gagliardo LF, Lee NA, Lee JJ, Appleton JA (2012) Eosinophils preserve parasitic nematode larvae by regulating local immunity. J Immunol 188:17–425CrossRefGoogle Scholar
  30. Gill HS, Altmann K, Cross ML, Husband AJ (2000) Induction of T helper 1 and T helper 2 type immune responses during Haemonchus contortus infection in sheep. Immunology 99:458–463CrossRefGoogle Scholar
  31. González JF, Molina JM, Ruiz A, Conde de Felipe MM, Rodríguez- Ponee E (2003) The immune response against gastrointestinal nematodes in ruminants: a review. Rev Iber Parasitol 63:97–115Google Scholar
  32. González-Garduño R, Arellano MEL, Mendoza de Gives P, García JA, Magdeleine CM, Hernández GT, Hernández JO, Hinojosa-Cuéllar JA (2017) Comparative response of IgA and IgG activity and hematological parameters among four main beef-cattle breeds infected with gastrointestinal nematodes in the warm humid tropic of Mexico. Ann Anim Sci 17:819–833CrossRefGoogle Scholar
  33. Grencis RK, Humphreys NE, Bancroft AL (2014) Immunity to gastrointestinal nematodes: mechanisms and myths. Immunol Rev 260:183–205CrossRefGoogle Scholar
  34. Halliday AM, Routledge CM, Smith SK, Matthews JB, Smith WD (2007) Parasite loss and inhibited development of Teladorsagia circumcincta in relation to the kinetics of the local IgA response in sheep. Parasite Immunol 29:425–434CrossRefGoogle Scholar
  35. Harriman GR, Kunimoto DY, Elliott JF, Paetkau V, Strober W (1988) The role of IL-5 in IgA B cell differentiation. J Immunol 140:3033–3039PubMedGoogle Scholar
  36. Henderson NG, Stear MJ (2006) Eosinophils and IgA responses in sheep infected with Teladorsagia circumcincta. Vet Immunol Immunopathol 112:62–66CrossRefGoogle Scholar
  37. Hilderson H, Vercruysse J, Clearebout E, De Graaf DC, Fransen J, Berghen B (1995) Interactions between Ostertagia ostertagi and Cooperia oncophora in calves. Vet Parasitol 56:107–119CrossRefGoogle Scholar
  38. Hou Y, Liu GE, Bickhart DM, Matukumalli LK, Li C, Song J, Gasbarre LC, Van Tasel CP, Sonstegard TS (2012) Genomic regions showing copy number variations associate with resistance or susceptibility to gastrointestinal nematodes in Angus cattle. Funct Integr Genomics 12:81–92CrossRefGoogle Scholar
  39. Huang L, Appleton JA (2016) Eosinophil in helminth infection: defender and dupes. Trends Parasitol 32:798–807CrossRefGoogle Scholar
  40. Huntley JF, PattersonM MackellarA, JacksonF StevensonLM, Coop RL (1995) A comparison of the mast cell and eosinophil responses of sheep and goats to gastrointestinal nematode infections. Res Vet Sci 58:5–10CrossRefGoogle Scholar
  41. Kandil OM, Eid NA, Elakabawy LM, Abdelrahman KA, Helal MA (2015) Immunodiagnostic potency of different Haemonchus contortus antigens for diagnosis of experimentally and naturally haemonchosis in Egyptian sheep. APG 6:238–247Google Scholar
  42. Kandil OM, Hendawy SHM, El Namaky AH, Gabrashanska MP, Nanev VN (2016) Evaluation of different Haemonchus contortus antigens for diagnosis of sheep haemonchosis by ELISA and their cross reactivity with other helminthes. J Parasit Dis. CrossRefPubMedPubMedCentralGoogle Scholar
  43. Kandil OM, Abdelrahman KA, Shalaby HA, Hendawy SHM, Abu El Ezz NMT, Nassar SA, Miller JE (2017) Evaluation of crude larval protein and recombinant somatic protein 26/23 (rHcp26/23) immunization against Haemonchus contortus in sheep. Vet World 10:758–763CrossRefGoogle Scholar
  44. Khalafalla RE, Elseify MA, Elbahy NM (2011) Seasonal prevalence of gastrointestinal nematode parasites of sheep in Northern region of Nile Delta, Egypt. Parasitol Res 108:337–340CrossRefGoogle Scholar
  45. Komai-Koma M, Ds Gilchrist, McKenzie ANJ, Goodyear CS, Xu D, Liew FY (2011) IL-33 activates B1 cells and exacerbates contact sensitivity. J Immunol 186:2584–2591CrossRefGoogle Scholar
  46. Kooyman FN, Schallig HD, Van Leeuwen MA, MacKellar A, Huntley JF, Cornelissen AW, Vervelde L (2000) Protection in lambs vaccinated with Haemonchus contortus antigens is age related and correlates with IgE rather than IgG1 antibody. Parasite Immunol 22:13–20CrossRefGoogle Scholar
  47. Lacroux C, Nguyen THC, Andreoletti O, Prevot F, Grisez C, Bergeaud J, Gruner L, Brunel J, Francois D, Dorchies P, Jacquiet P (2006) Haemonchus contortus (Nematoda: Trichostrongylidae) infection in lambs elicits an unequivocal Th2 immune response. Vet Res 37:607–622CrossRefGoogle Scholar
  48. Mahmoud MA, Amin MM, Youssef RR, El-Kattan A, Goda ASA, Abou El-Naga TR (2008) Studies on some endoparasites of camels in the Southeastern area of Egypt. SCVMJ 13:81–92Google Scholar
  49. Martínez-Ortíz-de-Montellano C, Vargas-Magaña JJ, Canul-Ku HL, Miranda-Soberanis R, Capetillo-Leal C, Sandoval-Castro CA, Hoste H, Torres-Acosta JFJ (2010) Effect of a tropical tannin-rich plant Lysiloma latisiliquum on adult populations of Haemonchus contortus in sheep. Vet Parasitol 172:283–290CrossRefGoogle Scholar
  50. McRae KM, Good B, Hanrahan JP (2014) Response to Teladorsagia circumcincta infection in Scottish Blackface lambs with divergent phenotypes for nematode resistance. Vet Parasitol 206:200–207CrossRefGoogle Scholar
  51. McRae KM, Stear MJ, Good B, Keane OM (2015) The host immune response to gastrointestinal nematode infection in sheep. Parasite Immunol 37:605–613CrossRefGoogle Scholar
  52. Meeusen ENT, Balic A (2000) Do eosinophils have a role in the killing of helminth parasites? Parasitol Today 16:95–101CrossRefGoogle Scholar
  53. Meeusen ENT, Piedrafita D (2003) Exploiting natural immunity to helminth parasites for the development of veterinary vaccines. Int J Parasitol 33:1285–1290CrossRefGoogle Scholar
  54. Meeusen ENT, Balic A, Bowles V (2005) Cells, cytokines and other molecules associated with rejection of gastrointestinal nematode parasites. Vet Immunol Immunopathol 108:121–125CrossRefGoogle Scholar
  55. Miller HRP (1996) Mucosal mast cells and the allergic response against nematode parasites. Vet Immunol Immunopathol 54:331–336CrossRefGoogle Scholar
  56. Miller JE, Horohov DW (2006) Immunological aspects of nematode parasite control in sheep. J Anim Sci 84:124–132CrossRefGoogle Scholar
  57. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969CrossRefGoogle Scholar
  58. Ortolani EL, Leal ML, Minervino AHH, Aires AR, Coop RL, Jackson F, Suttle NF (2013) Effects of parasitism on cellular immune response in sheep experimentally infected with Haemonchus contortus. Vet Parasitol 196:230–234CrossRefGoogle Scholar
  59. Pernthaner A, Cole SA, Morrison L, Hein WR (2005) Increased expression of interleukin-5 (IL-5), IL-13, and tumor necrosis factor alpha genes in intestinal lymph cells of sheep selected for enhanced resistance to nematodes during infection with Trichostrongylus colubriformis. Infect Immun 73:2175–2183CrossRefGoogle Scholar
  60. Pettit JJ, Jackson F, Rocchi M, Huntley JF (2005) The relationship between responsiveness against gastrointestinal nematodes in lambs and the numbers of circulating IgE-bearing cells. Vet Parasitol 134:131–139CrossRefGoogle Scholar
  61. Pisseri F, De Benedictis C, Roberti di Sarsina P, Azzarello B (2013) Sustainable animal production, systemic prevention strategies in parasitic diseases of ruminants. Altern Integ Med 2:2–7Google Scholar
  62. Ploeger HW, Kloosterman A, Rietveld FW (1995) Acquired immunity against Cooperia spp. and Ostertagia spp. in calves: effect of level of exposure and timing of the midsummer increase. Vet Parasitol 58:61–74CrossRefGoogle Scholar
  63. Prada JCJ, Stear MJ, Mair C, Singleton D, Stefan T, Stear A, Marion G, Matthews L (2014) An explicit immunogenic model of gastrointestinal nematode infection in sheep. J R Soc Interface 11:20140416CrossRefGoogle Scholar
  64. Premier RR, Jacobs HJ, Lofthouse SA, Sedgmen BJ, Meeusen ENT (2004) Antibody isotype profiles in serum and circulating antibody-secreting cells following mucosal and peripheral immunisations of sheep. Vet Immunol Immunopathol 98:77–84CrossRefGoogle Scholar
  65. Quintana JF, Makepeace BL, Babayan SA, Ivens A, Pfarr KM, Blaxter M, Debrah A, Wanji S, Ngangyung HF, Bah GS (2015) Extracellular Onchocerca-derived small RNAs in host nodules and blood. Parasit Vectors 8:58–69CrossRefGoogle Scholar
  66. Ramos F, Portella LP, Rodrigues FS, Reginato CZ, Potter L, Cezar AS, Sangioni LA, Vogel FSF (2016) Anthelmintic resistance of gastrointestinal nematodes of beef cattle in the state of Rio Grande do Sul, Brazil. Int J Parasitol Drugs Drug Resist 6:93–101CrossRefGoogle Scholar
  67. Rodrigues GC, Vale VLC, Silva MC, Sales TS, Raynal JT, Pimentel ACM, Trindade SC, Meyer RJ (2017) Immune response against Haemonchus contortus and the Th1-Th2 paradigm in helminth infection. EC Microbiol 9:152–159Google Scholar
  68. Rothwell TLW (1989) Immune expulsion of parasitic nematodes from the alimentary tract. Int J Parasitol 19:139–168CrossRefGoogle Scholar
  69. Shakya KP, Miller JE, Horohov DW (2009) A Th2 type of immune response is associated with increased resistance to Haemonchus contortus in naturally infected Gulf Coast Native lambs. Vet Parasitol 163:57–66CrossRefGoogle Scholar
  70. Shalaby HA (2013) Anthelmintic resistance; how to overcome it? Iran J Parasitol 8:18–32PubMedPubMedCentralGoogle Scholar
  71. Shaw RJ, Gatehouse TK, McNeill MM (1998) Serum IgE responses during primary and challenge infections of sheep with Trichostrongylus colubriformis. Int J Parasitol 28:293–302CrossRefGoogle Scholar
  72. Shin MH, Lee YA, Min DY (2009) Eosinophil-mediated tissue inflammatory responses in helminth infection. Korean J Parasitol 47:125–131CrossRefGoogle Scholar
  73. Sobhy SG (2005) Some studies in helminth parasites of abomasum of cattle and buffaloes in Kafr-Elsheikh province. M.V.Sc. Thesis, Kafr-Elsheikh UniversityGoogle Scholar
  74. Soli F, Terrill TH, Shaik SA, Getz WR, Miller JE, Vanguru M, Burke JM (2010) Efficacy of copper oxide wire particles against gastrointestinal nematodes in sheep and goats. Vet Parasitol 168:93–96CrossRefGoogle Scholar
  75. Sorci G, Cornet S, Faivre B (2013) Immune evasion, immunopathology and the regulation of the immune system. Pathogens 2:71–91CrossRefGoogle Scholar
  76. Souza BMPS, Lambert SM, Nishi SM, Benavides MV, Berne MEA, Madruga CR, Almeida MAO (2015) Galectins and collectinis expression are increased in Haemonchus contortus infected Corriedale sheep. Rev Bras Parasitol Vet 24:317–323CrossRefGoogle Scholar
  77. Sutherland IA, Brown AE, Green RS, Miller CM, Leathwick DM (1999) The immune response of sheep to larval challenge with Ostertagia circumcincta and Ostertagia ostertagi. Vet Parasitol 84:125–135CrossRefGoogle Scholar
  78. Sykes AR, Coop RL (2001) Interaction between nutrition and gastrointestinal parasitism in sheep. N Z Vet J 49:222–226CrossRefGoogle Scholar
  79. Torres-Acosta FFJ (2003) The effect of supplementary feeding in browsing Criollo kids and Hair sheep naturally infected with gastrointestinal nematodes. In: 6th international symposium on the nutrition of herbivores, Mérida, Mexico, pp 18–24Google Scholar
  80. Toscan G, Cadore GC, Limana JFT, Weber A, Palma HH, Duarte MMF, Sangioni LA, Vogel FSF (2017) Immune response of sheep naturally infected with Haemonchus spp. on pastures with two different nutritional conditions. Semin Cienc Agrar 38:809–819CrossRefGoogle Scholar
  81. Werling D, Piercy J, Coffey TJ (2006) Expression of toll-like receptors (TLR) by bovine antigen presenting cells—potential role in pathogen discrimination. Veterinary Immunol Immunopathol 112:2–11CrossRefGoogle Scholar
  82. Zvinorova PI, Halimani TE, Muchadeyi FC, Matika O, Riggio V, Dzama K (2016) Breeding for resistance to gastrointestinal nematodes—the potential in low—input/output small ruminant production system. Vet Parasitol 225:19–28CrossRefGoogle Scholar

Copyright information

© Indian Society for Parasitology 2018

Authors and Affiliations

  1. 1.Parasitology and Animal Diseases Department, Veterinary Research DivisionNational Research CentreGizaEgypt

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