Recent Progress in Understanding Host Mucosal Response to Avian Coccidiosis and Development of Alternative Strategies to Mitigate the Use of Antibiotics in Poultry Production

  • Lillehoj, Hyun-Soon (Animal Parasitic Diseases Laboratory, Animal and Natural Resources Institute, Department of Agriculture-Agricultural Research Service) ;
  • Lee, Sung-Hyen (Animal Parasitic Diseases Laboratory, Animal and Natural Resources Institute, Department of Agriculture-Agricultural Research Service) ;
  • Jang, Seung-Ik (Animal Parasitic Diseases Laboratory, Animal and Natural Resources Institute, Department of Agriculture-Agricultural Research Service) ;
  • Kim, Duk-Kyung (Animal Parasitic Diseases Laboratory, Animal and Natural Resources Institute, Department of Agriculture-Agricultural Research Service) ;
  • Lee, Kyung-Woo (Animal Parasitic Diseases Laboratory, Animal and Natural Resources Institute, Department of Agriculture-Agricultural Research Service)
  • Received : 2001.09.10
  • Accepted : 2011.10.05
  • Published : 2011.12.31


As the world population grows and developing countries become more affluent, the global consumption of meat will increase by more than 50% within the next 10 years. Confronting the increased demand for poultry food products are emerging field diseases, increasing regulatory bans of antimicrobial growth promoters, high-density growth conditions, and waste management. Although biotechnology offers solutions to some of these challenges, basic studies are needed to better understand the complex interaction between the intestinal microbiome, host immunity and the environment. This presentation will focus on emerging strategies to enhance gut immunity and to decrease economic losses due to poultry diseases. This presentation will highlight recent developments in coccidiosis research and provide information on host immunity, immunomodulation, and the latest advances in dietary and nutritional approaches against coccidiosis. Such information will magnify our understanding of host-parasite biology, mucosal immunology, and design of future nutritional interventions and vaccination strategies for coccidiosis.



  1. Avery S, Rothwell L, Degen WD, Schijns VE, Young J, Kaufman J, Kaiser P 2004 Characterization of the first nonmammalian T2 cytokine gene cluster: the cluster contains functional single-copy genes for IL-3, IL-4, IL-13, and GM-CSF, a gene for IL-5 that appears to be a pseudogene, and a gene encoding another cytokine like transcript, KK34. J Interferon Cytokine Res 24:600-610.
  2. Bessay M, Le Vern Y, Kerboeuf D, Yvore P, Quere P 1996 Changes in intestinal intra-epithelial and systemic T-cell subpopulations after an Eimeria infection in chickens: comparative study between E. acervulina and E. tenella. Vet Res 27:503-514.
  3. Bliss TW, Dohms JE, Emara MG, Keeler CL 2005 Gene expression profiling of avian macrophage activation. Vet Immunol Immunopathol 105:289-299.
  4. Breed DG, Dorrestein J, Schetters TP, Waart LV, Rijke E, Vermeulen AN 1997b Peripheral blood lymphocytes from Eimeria tenella infected chickens produce gamma-interferon after stimulation in vitro. Parasite Immunol 19:127-135.
  5. Breed DG, Dorrestein J, Vermeulen AN 1996 Immunity to Eimeria tenella in chickens: phenotypical and functional changes in peripheral blood T-cell subsets. Avian Dis 40:37-48.
  6. Breed DG, Schetters TP, Verhoeven NA, Vermeulen AN 1997a Characterization of phenotype related responsiveness of peripheral blood lymphocytes from Eimeria tenella infected chickens. Parasite Immunol 19:563-569.
  7. Burnside J, Neiman P, Tang J, Basom R, Talbot R, Aronszajn M, Burt D, Delrow J 2005 Development of a cDNA array for chicken gene expression analysis. BMC Genomics 6:13.
  8. Byrnes S, Eaton R, Kogut M 1993 In vitro interleukin-1 and tumor necrosis factor-alpha production by macrophages from chickens infected with either Eimeria maxima or Eimeria tenella. Int J Parasitol 23:639-645.
  9. Choi KD, Lillehoj HS 2000 Role of chicken IL-2 on gammadelta T-cells and Eimeria acervulina-induced changes in intestinal IL-2 mRNA expression and gammadelta T-cells. Vet Immunol Immunopathol 73:309-321.
  10. Choi KD, Lillehoj HS, Zalenga DS 1999 Changes in local IFN-gamma and TGF-beta4 mRNA expression and intraepithelial lymphocytes following Eimeria acervulina infection. Vet Immunol Immunopathol 71:263-275.
  11. Cogburn LA, Wang X, Carre W, Rejto L, Aggrey SE, Duclos MJ, Simon J, Porter TE 2004 Functional genomics in chickens: development of integrated-systems microarrays for transcriptional profiling and discovery of regulatory pathways. Comp Funct Genomics 5:253-261.
  12. Dalloul RA, Bliss TW, Hong YH, Ben-Chouikha I, Park DW, Keeler CL, Lillehoj HS 2007 Unique responses of the avian macrophage to different species of Eimeria. Mol Immunol 44:558-566.
  13. Degen WG, Van Daal N, Van Zuilekom HI, Burnside J, Schijns VE 2004 Identification and molecular cloning of functional chicken IL-12. J Immunol 172:4371-4380.
  14. Digby MR, Lowenthal JW 1995 Cloning and expression of the chicken interferon-gamma gene. J Interferon Cytokine Res 15:939-945.
  15. Hong YH, Lillehoj HS, Dalloul RA, Min W, Miska KB, Tuo W, Lee SH, Han JY, Lillehoj EP 2006 Molecular cloning and characterization of chicken NK-lysin. Vet Immunol Immunopathol 110:339-347.
  16. Kaiser P, Hughes S, Bumstead N 1999 The chicken 9E3/CEF4 CXC chemokine is the avian orthologue of IL8 and maps to chicken chromosome 4 syntenic with genes flanking the mammalian chemokine cluster. Immunogenetics 49:673-684.
  17. Kim CH, Lillehoj HS, Bliss TW, Keeler CL, Hong YH, Park DW, Yamage M, Min W, Lillehoj EP 2008a Construction and application of an avian intestinal intraepithelial lymphocyte cDNA microarray (AVIELA) for gene expression profiling during Eimeria maxima infection. Vet Immunol Immunopathol 124:341-354.
  18. Kim CH, Lillehoj HS, Hong YH, Keeler CL, Lillehoj EP 2010a Comparison of global transcriptional responses to primary and secondary Eimeria acervulina infections in chickens. Dev Comp Immunol 34:344-351.
  19. Kim DK, Lillehoj HS, Hong YH, Park DW, Lamont SJ, Han JY, Lillehoj EP 2008b Immune-related gene expression in two B-complex disparate genetically inbred Fayoumi chicken lines following Eimeria maxima infection. Poultry Sci 87:433-443.
  20. Kim DK, Lillehoj HS, Lee SH, Jang SI, Bravo D 2010b High- throughput gene expression analysis of intestinal intraepithelial lymphocytes after oral feeding of carvacrol, cinnamaldehyde, or Capsicum oleoresin. Poultry Sci 89:68-81.
  21. Koskela K, Kohonen P, Salminen H, Uchida T, Buerstedde JM, Lassila O 2004 Identification of a novel cytokine-like transcript differentially expressed in avian gammadelta T cells. Immunogenetics 55:845-854.
  22. Lee SH, Lillehoj HS, Cho SM, Chun HK, Park HJ, Lim CI, Lillehoj EP 2009b Immunostimulatory effects of oriental plum (Prunus salicina Lindl.). Comp Immunol Microbiol Infect Dis 32:407-417
  23. Lee SH, Lillehoj HS, Cho SM, Park DW, Hong YH, Lillehoj EP, Heckert RA, Park HJ Chun HK 2009c Protective effects of dietary safflower (Carthamus tinctorius) on experimental coccidiosis. J Poult Sci 46:155-162.
  24. Lee SH, Lillehoj HS, Chun HK, Park HJ, Cho SM Lillehoj EP 2009a In vitro effects of methanol extracts of Korean medicinal fruits (persimmon, raspberry, tomato) on chicken lymphocytes, macrophages, and tumor cells. J Poult Sci 46:149-154.
  25. Lee SH, Lillehoj HS, Chun HK, Tuo W, Park HJ, Cho SM, Lee YM, Lillehoj EP 2007 In vitro treatment of chicken peripheral blood lymphocytes, macrophages, and tumor cells with extracts of Korean medicinal plants. Nutr Res 27:362-366.
  26. Lee SH, Lillehoj HS, Heckert RA, Cho SM, Tuo W, Lillehoj EP, Chun HK, Park HJ 2008a Immune enhancing properties of safflower leaf (Carthamus tinctorius) on chicken lymphocytes and macrophages. J Poult Sci 45:147-151.
  27. Lee SH, Lillehoj HS, Hong YH, Jang SI, Lillehoj EP, Ionescu C, Mazuranok CL, Bravo D 2010a In vitro effects of plant and mushroom extracts on immunological function of chicken lymphocytes and macrophages. Br Poult Sci 51:213-221.
  28. Lee SH, Lillehoj HS, Jang SI, Kim DK, Ionescu C, Bravo D 2010b Effect of dietary curcuma, capsicum, and lentinus, on enhancing local immunity against Eimeria acervulina infection. J Poult Sci 47:89-95.
  29. Lee SH, Lillehoj HS, Jang SI, Lee KW, Bravo D, Lillehoj EP 2011b Effects of dietary supplementation with phytonutrients on vaccine-stimulated immunity against infection with Eimeria tenella. Vet Parasitol 181:97-105.
  30. Lee SH, Lillehoj HS, Jang SI, Lee KW, Park MS, Lillehoj EP, Bravo D 2011a Cinnamaldehyde enhances in vitro parameters of immunity and reduces in vivo infection against avian coccidiosis. Brit J Nutr 106:862-869.
  31. Lee SH, Lillehoj HS, Lillehoj EP, Cho SM, Park DW, Hong YH, Chun HK, Park HJ 2008b Immunomodulatory properties of dietary plum on coccidiosis. Comp Immunol Microbiol Infect Dis 31:389-402.
  32. Leslie GA, Clem LW 1969 Phylogen of immunoglobulin structure and function. 3.3 Immunoglobulins of the chicken. J Exp Med 130:1337-1352.
  33. Lillehoj HS 1986 Immune response during coccidiosis in SC and FP chickens. I. In vitro assessment of T cell proliferation response to stage-specific parasite antigens. Vet Immunol Immunopathol 13:321-330.
  34. Lillehoj HS 1988 Influence of inoculation dose, inoculation schedule, chicken age, and host genetics on disease susceptibility and development of resistance to Eimeria tenella infection. Avian Dis 32:437-444.
  35. Lillehoj HS, Bacon LD 1991 Increase of intestinal intraepithelial lymphocytes expressing CD8 antigen following challenge infection with Eimeria acervulina. Avian Dis 35:294-301.
  36. Lillehoj HS, Choi KD 1998 Recombinant chicken interferongamma- mediated inhibition of Eimeria tenella development in vitro and reduction of oocyst production and body weight loss following Eimeria acervulina challenge infection. Avian Dis 42:307-314.
  37. Lillehoj HS, Choi KD, Jenkins MC, Vakharia VN, Song KD, Han JY, Lillehoj EP 2000 A recombinant Eimeria protein inducing interferon-gamma production: Comparison of different gene expression systems and immunization strategies for vaccination against coccidiosis. Avian Dis 44:379-389.
  38. Lillehoj HS, Kang SY, Keller L, Sevoian M 1989a Eimeria tenella and E. acervulina: lymphokines secreted by an avian T cell lymphoma or by sporozoite-stimulated immune T lymphocytes protect chickens against avian coccidiosis. Exp Parasitol 69:54-64.
  39. Lillehoj HS, Kim CH, Keeler CL, Zhang S 2007 Immunogenomic approaches to study host immunity to enteric pathogens. Poultry Sci 86:1491-1500.
  40. Lillehoj HS, Lillehoj EP 2000 Avian coccidiosis. A review of acquired intestinal immunity and vaccination strategies. Avian Dis 44:408-425.
  41. Lillehoj HS, Min W, Choi KD, Babu US, Burnside J, Miyamoto T, Rosenthal BM, Lillehoj EP 2001 Molecular, cellular, and functional characterization of chicken cytokines homologous to mammalian IL-15 and IL-2. Vet Immunol Immunopathol 82:229-244.
  42. Lillehoj HS, Min W, Dalloul RA 2004 Recent progress on the cytokine regulation of intestinal immune responses to Eimeria. Poultry Sci 83:611-623.
  43. Lillehoj HS, Ruff MD 1987 Comparison of disease susceptibility and subclass-specific antibody response in SC and FP chickens experimentally inoculated with Eimeria tenella, E. acervulina, or E. maxima. Avian Dis 31:112-119.
  44. Lillehoj HS, Ruff MD, Bacon LD, Lamont SJ, Jeffers TK 1989b Genetic control of immunity to Eimeria tenella. Interaction of MHC genes and non-MHC linked genes influences levels of disease susceptibility in chickens. Vet Immunol Immunopathol 20:135-148.
  45. Lillehoj HS, Trout JM 1996 Avian gut-associated lymphoid tissues and intestinal immune responses to Eimeria parasites. Clin Microbiol Rev 9:349-360.
  46. Lynagh GR, Bailey M, Kaiser P 2000 Interleukin-6 is produced during both murine and avian Eimeria infections. Vet Immunol Immunopathol 76:89-102.
  47. Min W, Lillehoj HS 2002 Isolation and characterization of chicken interleukin-17 cDNA. J Interferon Cytokine Res 22:1123-1128.
  48. Min W, Lillehoj HS 2004 Identification and characterization of chicken interleukin-16 cDNA. Dev Comp Immunol 28:153-162.
  49. Min W, Lillehoj HS, Ashwell CM, Van Tassell CP, Dalloul RA, Matukumalli LK, Han JY, Lillehoj EP 2005 Expressed sequence tag analysis of Eimeria-stimulated intestinal intraepithelial lymphocytes in chickens. Mol Biotechnol 30:43-150.
  50. Min W, Lillehoj HS, Burnside J, Weining KC, Staeheli P, Zhu JJ 2001 Adjuvant effects of IL-1beta, IL-2, IL-8, IL-15, IFN-alpha, IFN-gamma TGF-beta4 and lymphotactin on DNA vaccination against Eimeria acervulina. Vaccine 20:267-274.
  51. Min W, Lillehoj HS, Kim S, Zhu JJ, Beard H, Alkharouf N, Matthews BF 2003 Profiling local gene expression changes associated with Eimeria maxima and Eimeria acervulina using cDNA microarray. Appl Microbiol Biotechnol 62:92-399.
  52. Morgan RW, Sofer L, Anderson AS, Bernberg EL, Cui J, Burnside J 2001 Induction of host gene expression following infection of chicken embryo fibroblasts with oncogenic Marek's disease virus. J Virol 75:533-539.
  53. Neiman PE, Grbic JJ, Polony TS, Kimmel R, Bowers SJ, Delrow J, Beemon KL 2003 Functional genomic analysis reveals distinct neoplastic phenotypes associated with cyb mutation in the bursa of Fabricius. Oncogene 22:1073-086.
  54. Parvari R, Avivi A, Lentner F, Ziv E, Tel-Or S, Burstein Y, Schechter I 1988 Chicken immunoglobulin gamma-heavy chains: limited VH gene repertoire, combinatorial diversification by D gene segments and evolution of the heavy chain locus. EMBO J 7:739-744.
  55. Rose ME, Hesketh P 1982 Immunity to coccidia in chickens: adoptive transfer with peripheral blood lymphocytes and spleen cells. Parasite Immunol 4:171-185.
  56. Rothwell L, Young JR, Zoorob R, Whittaker CA, Hesketh P, Archer A, Smith AL, Kaiser P 2004 Cloning and characterization of chicken IL-10 and its role in the immune response to Eimeria maxima. J Immunol 173:2675-2682.
  57. Schneider K, Klaas R, Kaspers B, Staeheli P 2001 Chicken interleukin-6 cDNA structure and biological properties. Eur J Biochem 268:4200-4206.
  58. Schneider K, Puehler F, Baeuerle D, Elvers S, Staeheli P, Kaspers B, Weining KC 2000 cDNA cloning of biologically active chicken interleukin-18. J Interferon Cytokine Res 20:879-883.
  59. Sick C, Schneider K, Staeheli P, Weining KC 2000 Novel chicken CXC and CC chemokines. Cytokine 12:181-186.
  60. Song KD, Lillehoj HS, Choi KD, Zarlenga D, Han JY 1997 Expression and functional characterization of recombinant chicken interferon-gamma. Vet Immunol Immunopathol 58:321-333.
  61. Staeheli P, Puehler F, Schneider K, Gobel TW, Kaspers B 2001 Cytokines of birds: conserved functions-a largely different look. J Interferon Cytokine Res 21:993-1010.
  62. Sundick RS, Gill-Dixon C 1997 A cloned chicken lymphokine homologous to both mammalian IL-2 and IL-15. J Immunol 159:720-725.
  63. Trout JM, Lillehoj HS 1996 T lymphocyte roles during Eimeria acervulina and Eimeria tenella infections. Vet Immunol Immunopathol 53:163-172.
  64. Vervelde L, Vermeulen AN, Jeurissen SH 1996 In situ characterization of leucocyte subpopulations after infection with Eimeria tenella in chickens. Parasite Immunol 18:47-256.
  65. Yun CH, Lillehoj HS, Choi KD 2000a Eimeria tenella infection induces local gamma interferon production and intestinal lymphocyte subpopulation changes. Infect Immun 68:1282-1288.
  66. Yun CH, Lillehoj HS, Zhu J, Min W 2000b Kinetic differences in intestinal and systemic interferon-gamma and antigen-specific antibodies in chickens experimentally infected with Eimeria maxima. Avian Dis 44:305-312.

Cited by

  1. Development of immunization trials against Eimeria spp. vol.5, 2016,
  2. Recent progress in host immunity to avian coccidiosis: IL-17 family cytokines as sentinels of the intestinal mucosa vol.41, pp.3, 2013,