Analyze Diet
Clinical and diagnostic laboratory immunology2003; 10(3); 345-351; doi: 10.1128/cdli.10.3.345-351.2003

Immunoglobulin G subisotype responses of pneumonic and healthy, exposed foals and adult horses to Rhodococcus equi virulence-associated proteins.

Abstract: Rhodococcus equi causes severe pyogranulomatous pneumonia in foals and in immunocompromised humans. Replication of virulent isolates within macrophages correlates with the presence of a large plasmid which encodes a family of seven virulence-associated proteins (VapA and VapC to VapH), whose functions are unknown. Although cell-mediated immunity is thought to be crucial in eliminating R. equi infection, antibody partially protects foals. The antibody response to both VapA and VapC was similar in six adult horses and six naturally exposed but healthy foals, as well as in eight foals with R. equi pneumonia. The immunoglobulin G (IgG) subisotype response of pneumonic foals to Vap proteins was significantly IgGb biased and also had a trend toward higher IgGT association compared to the isotype association of antibody in adult horses and healthy exposed foals. This suggests that in horses, IgGb and IgGT are Th2 isotypes and IgGa is a Th1 isotype. Furthermore, it suggests that foals which develop R. equi pneumonia have a Th2-biased, ineffective immune response whereas foals which become immune develop a Th1-biased immune response. Pneumonic foals had significantly more antibody to VapD and VapE than did healthy exposed foals. This may indicate a difference in the expression of these two Vap proteins during persistent infection. Alternatively, in pneumonic foals the deviation of the immune response toward VapD and VapE may reflect a bias unfavorable to R. equi resistance. These data indicate possible age-related differences in the equine immune response affecting Th1-Th2 bias as well as antibody specificity bias, which together favor the susceptibility of foals to R. equi pneumonia.
Publication Date: 2003-05-10 PubMed ID: 12738629PubMed Central: PMC154967DOI: 10.1128/cdli.10.3.345-351.2003Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper investigates the response of the immune system in horses, specifically foals, to Rhodococcus equi – a cause of serious pneumonia. The study looks at how the body produces specific types of antibodies in response to this infection and how these production patterns may indicate the efficiency of the immune response.

Understanding the Research Context

  • Rhodococcus equi is a bacterium that causes a severe form of pneumonia, notably in foals (young horses) and immunocompromised humans. It survives and replicates within cells called macrophages.
  • The virulence (severity of disease it can cause) of R. equi is associated with a large plasmid – a piece of genetic material – that encodes a family of seven virulence-associated proteins (VapA and VapC to VapH).
  • While it is understood that cell-mediated immunity – immune responses that involve T cells rather than antibodies – play a key role in combating R. equi, it has been observed that antibodies can also provide some protection, particularly in foals.

Key Findings

  • The research found that the antibody response to two types of virulence-associated proteins (VapA and VapC) were similar in both adult horses, healthy foals, and foals with R. equi pneumonia.
  • However, it was noted that the pneumonic foals showed a strong response in producing immunoglobulin G (IgG) antibodies, specifically the IgGb subtype, towards the Vap proteins. There was also a slight increase in the connection to the IgGT subtype compared to healthy foals and adult horses. This signpost that in horses, IgGb and IgGT are Th2 isotypes while IgGa is a Th1 isotype, which play different roles in the immune response.
  • Additionally, foals with pneumonia were found to have more antibodies against two other virulence-associated proteins (VapD and VapE) compared to healthy foals. This difference could suggest these proteins are expressed more during chronic infection or that the immune response targeting these proteins is ineffective against R. equi.

Conclusion

  • The findings suggest that foals developing pneumonia show an ineffective Th2-biased immune response, whereas those foals that build immunity exhibit a Th1-biased immune response.
  • The research also hints at the possibility that age plays a role in shaping the immune response in horses, notably that younger horses (foals) may be more susceptible to R. equi pneumonia because of these differences in antibody production and immune response bias.

Cite This Article

APA
Hooper-McGrevy KE, Wilkie BN, Prescott JF. (2003). Immunoglobulin G subisotype responses of pneumonic and healthy, exposed foals and adult horses to Rhodococcus equi virulence-associated proteins. Clin Diagn Lab Immunol, 10(3), 345-351. https://doi.org/10.1128/cdli.10.3.345-351.2003

Publication

ISSN: 1071-412X
NlmUniqueID: 9421292
Country: United States
Language: English
Volume: 10
Issue: 3
Pages: 345-351

Researcher Affiliations

Hooper-McGrevy, Kathleen E
  • Department of Pathobiology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Wilkie, Bruce N
    Prescott, John F

      MeSH Terms

      • Age Factors
      • Animals
      • Antibody Formation
      • Bacterial Proteins / immunology
      • Horse Diseases / immunology
      • Horses
      • Immunoglobulin G / immunology
      • Immunoglobulin Isotypes / immunology
      • Pneumonia, Bacterial / immunology
      • Pneumonia, Bacterial / veterinary
      • Rhodococcus equi / immunology
      • Rhodococcus equi / pathogenicity
      • Th1 Cells / immunology
      • Th2 Cells / immunology
      • Virulence Factors / immunology

      References

      This article includes 48 references
      1. Adkins B. T-cell function in newborn mice and humans.. Immunol Today 1999 Jul;20(7):330-5.
        pubmed: 10379052doi: 10.1016/s0167-5699(99)01473-5google scholar: lookup
      2. Arlotti M, Zoboli G, Moscatelli GL, Magnani G, Maserati R, Borghi V, Andreoni M, Libanore M, Bonazzi L, Piscina A, Ciammarughi R. Rhodococcus equi infection in HIV-positive subjects: a retrospective analysis of 24 cases.. Scand J Infect Dis 1996;28(5):463-7.
        pubmed: 8953675doi: 10.3109/00365549609037941google scholar: lookup
      3. Balson, G. A., J. A. Yager, and B. A. Croy. 1992. SCID/beige mice in the study of immunity to Rhodococcus equi, p. 49-53. In P. D. Rossdale and J. F. Wade (ed.), Equine infectious diseases, 6th ed. R&W Publications, Newmarket, United Kingdom.
      4. Banks KL, McGuire TC. Surface receptors on neutrophils and monocytes from immunodeficient and normal horses.. Immunology 1975 Mar;28(3):581-8.
        pmc: PMC1445792pubmed: 1126740
      5. Bomford R. Will adjuvants be needed for vaccines of the future?. Dev Biol Stand 1998;92:13-7.
        pubmed: 9554255
      6. Brewer JM, Conacher M, Hunter CA, Mohrs M, Brombacher F, Alexander J. Aluminium hydroxide adjuvant initiates strong antigen-specific Th2 responses in the absence of IL-4- or IL-13-mediated signaling.. J Immunol 1999 Dec 15;163(12):6448-54.
        pubmed: 10586035
      7. Burton DR, Woof JM. Human antibody effector function.. Adv Immunol 1992;51:1-84.
        pubmed: 1502974doi: 10.1016/s0065-2776(08)60486-1google scholar: lookup
      8. Dijkstra CD, Döpp EA. Ontogenetic development of T- and B-lymphocytes and non-lymphoid cells in the white pulp of the rat spleen.. Cell Tissue Res 1983;229(2):351-63.
        pubmed: 6601989doi: 10.1007/bf00214978google scholar: lookup
      9. Donisi A, Suardi MG, Casari S, Longo M, Cadeo GP, Carosi G. Rhodococcus equi infection in HIV-infected patients.. AIDS 1996 Apr;10(4):359-62.
      10. Fernandez AS, Prescott JF, Nicholson VM. Protective effect against Rhodococcus equi infection in mice of IgG purified from horses vaccinated with virulence associated protein (VapA)-enriched antigens.. Vet Microbiol 1997 Jun 16;56(3-4):187-92.
        pubmed: 9226833doi: 10.1016/s0378-1135(97)00087-4google scholar: lookup
      11. Furesz SE, Wilkie BN, Mallard BA, Rosendal S, MacInnes JI. Anti-haemolysin IgG1 to IgG2 ratios correlate with haemolysin neutralization titres and lung lesion scores in Actinobacillus pleuropneumoniae infected pigs.. Vaccine 1998 Dec;16(20):1971-5.
        pubmed: 9796052doi: 10.1016/s0264-410x(98)00120-0google scholar: lookup
      12. Giguère S, Wilkie BN, Prescott JF. Modulation of cytokine response of pneumonic foals by virulent Rhodococcus equi.. Infect Immun 1999 Oct;67(10):5041-7.
      13. Harvey RL, Sunstrum JC. Rhodococcus equi infection in patients with and without human immunodeficiency virus infection.. Rev Infect Dis 1991 Jan-Feb;13(1):139-45.
        pubmed: 2017613doi: 10.1093/clinids/13.1.139google scholar: lookup
      14. Hooper-McGrevy KE, Giguere S, Wilkie BN, Prescott JF. Evaluation of equine immunoglobulin specific for Rhodococcus equi virulence-associated proteins A and C for use in protecting foals against Rhodococcus equi-induced pneumonia.. Am J Vet Res 2001 Aug;62(8):1307-13.
        pubmed: 11497456doi: 10.2460/ajvr.2001.62.1307google scholar: lookup
      15. Jefferis R, Kumararatne DS. Selective IgG subclass deficiency: quantification and clinical relevance.. Clin Exp Immunol 1990 Sep;81(3):357-67.
      16. Kanaly ST, Hines SA, Palmer GH. Failure of pulmonary clearance of Rhodococcus equi infection in CD4+ T-lymphocyte-deficient transgenic mice.. Infect Immun 1993 Nov;61(11):4929-32.
      17. Kanaly ST, Hines SA, Palmer GH. Cytokine modulation alters pulmonary clearance of Rhodococcus equi and development of granulomatous pneumonia.. Infect Immun 1995 Aug;63(8):3037-41.
      18. Kanaly ST, Hines SA, Palmer GH. Transfer of a CD4+ Th1 cell line to nude mice effects clearance of Rhodococcus equi from the lung.. Infect Immun 1996 Apr;64(4):1126-32.
      19. Kovarik J, Siegrist CA. Immunity in early life.. Immunol Today 1998 Apr;19(4):150-2.
        pubmed: 9577089doi: 10.1016/s0167-5699(97)01230-9google scholar: lookup
      20. Lopez AM, Hines MT, Palmer GH, Alperin DC, Hines SA. Identification of pulmonary T-lymphocyte and serum antibody isotype responses associated with protection against Rhodococcus equi.. Clin Diagn Lab Immunol 2002 Nov;9(6):1270-6.
      21. Marshall-Clarke S, Reen D, Tasker L, Hassan J. Neonatal immunity: how well has it grown up?. Immunol Today 2000 Jan;21(1):35-41.
        pubmed: 10637557doi: 10.1016/s0167-5699(99)01548-0google scholar: lookup
      22. McGuire, T. C., T. B. Crawford, and J. B. Henson. 1972. The isolation, characterization and functional properties of equine immunoglobulin classes and subclasses, p. 364-381. In J. T. Bryans and H. Gerber (ed.), Proceedings of the 3rd International Conference on Equine Infectious Diseases. S. Karger, Basel, Switzerland.
      23. Murray JS. How the MHC selects Th1/Th2 immunity.. Immunol Today 1998 Apr;19(4):157-63.
        pubmed: 9577091doi: 10.1016/s0167-5699(97)01237-1google scholar: lookup
      24. Namikawa R, Mizuno T, Matsuoka H, Fukami H, Ueda R, Itoh G, Matsuyama M, Takahashi T. Ontogenic development of T and B cells and non-lymphoid cells in the white pulp of human spleen.. Immunology 1986 Jan;57(1):61-9.
        pmc: PMC1453873pubmed: 3510968
      25. Nelson KM, Schram BR, McGregor MW, Sheoran AS, Olsen CW, Lunn DP. Local and systemic isotype-specific antibody responses to equine influenza virus infection versus conventional vaccination.. Vaccine 1998 Aug;16(13):1306-13.
        pubmed: 9682395doi: 10.1016/s0264-410x(98)00009-7google scholar: lookup
      26. Nordmann P, Ronco E, Nauciel C. Role of T-lymphocyte subsets in Rhodococcus equi infection.. Infect Immun 1992 Jul;60(7):2748-52.
      27. Patton S, Mock RE, Drudge JH, Morgan D. Increase of immunoglobulin T concentration in ponies as a response to experimental infection with the nematode Strongylus vulgaris.. Am J Vet Res 1978 Jan;39(1):19-23.
        pubmed: 75703
      28. Power CA, Wei G, Bretscher PA. Mycobacterial dose defines the Th1/Th2 nature of the immune response independently of whether immunization is administered by the intravenous, subcutaneous, or intradermal route.. Infect Immun 1998 Dec;66(12):5743-50.
      29. Prescott JF. Rhodococcus equi: an animal and human pathogen.. Clin Microbiol Rev 1991 Jan;4(1):20-34.
        pmc: PMC358176pubmed: 2004346doi: 10.1128/cmr.4.1.20google scholar: lookup
      30. Prescott JF, Nicholson VM, Patterson MC, Zandona Meleiro MC, Caterino de Araujo A, Yager JA, Holmes MA. Use of Rhodococcus equi virulence-associated protein for immunization of foals against R equi pneumonia.. Am J Vet Res 1997 Apr;58(4):356-9.
        pubmed: 9099378
      31. Proudman CJ, Trees AJ. Correlation of antigen specific IgG and IgG(T) responses with Anoplocephala perfoliata infection intensity in the horse.. Parasite Immunol 1996 Oct;18(10):499-506.
      32. Romagnani S. The Th1/Th2 paradigm.. Immunol Today 1997 Jun;18(6):263-6.
        pubmed: 9190109doi: 10.1016/s0167-5699(97)80019-9google scholar: lookup
      33. Ross TL, Balson GA, Miners JS, Smith GD, Shewen PE, Prescott JF, Yager JA. Role of CD4+, CD8+ and double negative T-cells in the protection of SCID/beige mice against respiratory challenge with Rhodococcus equi.. Can J Vet Res 1996 Jul;60(3):186-92.
        pmc: PMC1263831pubmed: 8809381
      34. Sheoran AS, Holmes MA. Separation of equine IgG subclasses (IgGa, IgGb and IgG(T)) using their differential binding characteristics for staphylococcal protein A and streptococcal protein G.. Vet Immunol Immunopathol 1996 Dec;55(1-3):33-43.
        pubmed: 9014304doi: 10.1016/s0165-2427(96)05618-8google scholar: lookup
      35. Sheoran AS, Sponseller BT, Holmes MA, Timoney JF. Serum and mucosal antibody isotype responses to M-like protein (SeM) of Streptococcus equi in convalescent and vaccinated horses.. Vet Immunol Immunopathol 1997 Nov;59(3-4):239-51.
        pubmed: 9477475doi: 10.1016/s0165-2427(97)00074-3google scholar: lookup
      36. Surcel HM, Troye-Blomberg M, Paulie S, Andersson G, Moreno C, Pasvol G, Ivanyi J. Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine response of blood lymphocytes to mycobacterial antigens.. Immunology 1994 Feb;81(2):171-6.
        pmc: PMC1422315pubmed: 8157267
      37. Takai S, Hines SA, Sekizaki T, Nicholson VM, Alperin DA, Osaki M, Takamatsu D, Nakamura M, Suzuki K, Ogino N, Kakuda T, Dan H, Prescott JF. DNA sequence and comparison of virulence plasmids from Rhodococcus equi ATCC 33701 and 103.. Infect Immun 2000 Dec;68(12):6840-7.
      38. Takai S, Koike K, Ohbushi S, Izumi C, Tsubaki S. Identification of 15- to 17-kilodalton antigens associated with virulent Rhodococcus equi.. J Clin Microbiol 1991 Mar;29(3):439-43.
        pmc: PMC269796pubmed: 2037660doi: 10.1128/jcm.29.3.439-443.1991google scholar: lookup
      39. Takai S, Nakata I, Fujui N, Kimura Y, Sasaki Y, Kakuda T, Tsubaki S, Kondo T, Sugiura T. Isotype-specific antibody responses to Rhodococcus equi in foals on a horse-breeding farm with a persistent incidence of R. equi infection. J. Equine Sci. 13:63-70.
      40. Takai S, Sekizaki T, Ozawa T, Sugawara T, Watanabe Y, Tsubaki S. Association between a large plasmid and 15- to 17-kilodalton antigens in virulent Rhodococcus equi.. Infect Immun 1991 Nov;59(11):4056-60.
      41. Tan C, Prescott JF, Patterson MC, Nicholson VM. Molecular characterization of a lipid-modified virulence-associated protein of Rhodococcus equi and its potential in protective immunity.. Can J Vet Res 1995 Jan;59(1):51-9.
        pmc: PMC1263734pubmed: 7704843
      42. Tkachuk-Saad O, Prescott J. Rhodococcus equi plasmids: isolation and partial characterization.. J Clin Microbiol 1991 Dec;29(12):2696-700.
      43. Victoratos P, Yiangou M, Avramidis N, Hadjipetrou L. Regulation of cytokine gene expression by adjuvants in vivo.. Clin Exp Immunol 1997 Sep;109(3):569-78.
      44. Wilsher ML, Hagan C, Prestidge R, Wells AU, Murison G. Human in vitro immune responses to Mycobacterium tuberculosis.. Tuber Lung Dis 1999;79(6):371-7.
        pubmed: 10694982doi: 10.1054/tuld.1999.0223google scholar: lookup
      45. Yager JA, Duder CK, Prescott JF, Zink MC. The interaction of Rhodococcus equi and foal neutrophils in vitro.. Vet Microbiol 1987 Aug;14(3):287-94.
        pubmed: 3672871doi: 10.1016/0378-1135(87)90116-7google scholar: lookup
      46. Yager JA, Prescott CA, Kramar DP, Hannah H, Balson GA, Croy BA. The effect of experimental infection with Rhodococcus equi on immunodeficient mice.. Vet Microbiol 1991 Aug 30;28(4):363-76.
        pubmed: 1949550doi: 10.1016/0378-1135(91)90071-mgoogle scholar: lookup
      47. Zink MC, Johnson JA, Prescot JF, Pascoe PJ. The interaction of Corynebacterium equi and equine alveolar macrophages in vitro.. J Reprod Fertil Suppl 1982;32:491-6.
        pubmed: 6962889
      48. Zink MC, Yager JA, Prescott JF, Fernando MA. Electron microscopic investigation of intracellular events after ingestion of Rhodococcus equi by foal alveolar macrophages.. Vet Microbiol 1987 Aug;14(3):295-305.
        pubmed: 3672872doi: 10.1016/0378-1135(87)90117-9google scholar: lookup

      Citations

      This article has been cited 14 times.
      1. Rocha JN, Dangott LJ, Mwangi W, Alaniz RC, Bordin AI, Cywes-Bentley C, Lawhon SD, Pillai SD, Bray JM, Pier GB, Cohen ND. PNAG-specific equine IgG(1) mediates significantly greater opsonization and killing of Prescottella equi (formerly Rhodococcus equi) than does IgG(4/7). Vaccine 2019 Feb 21;37(9):1142-1150.
        doi: 10.1016/j.vaccine.2019.01.028pubmed: 30691984google scholar: lookup
      2. Wright LM, Carpinone EM, Bennett TL, Hondalus MK, Starai VJ. VapA of Rhodococcus equi binds phosphatidic acid. Mol Microbiol 2018 Feb;107(3):428-444.
        doi: 10.1111/mmi.13892pubmed: 29205554google scholar: lookup
      3. Ramos HR, Junqueira-de-Azevedo Ide L, Novo JB, Castro K, Duarte CG, Machado-de-Ávila RA, Chavez-Olortegui C, Ho PL. A Heterologous Multiepitope DNA Prime/Recombinant Protein Boost Immunisation Strategy for the Development of an Antiserum against Micrurus corallinus (Coral Snake) Venom. PLoS Negl Trop Dis 2016 Mar;10(3):e0004484.
        doi: 10.1371/journal.pntd.0004484pubmed: 26938217google scholar: lookup
      4. Rocha JN, Cohen ND, Bordin AI, Brake CN, Giguère S, Coleman MC, Alaniz RC, Lawhon SD, Mwangi W, Pillai SD. Oral Administration of Electron-Beam Inactivated Rhodococcus equi Failed to Protect Foals against Intrabronchial Infection with Live, Virulent R. equi. PLoS One 2016;11(2):e0148111.
        doi: 10.1371/journal.pone.0148111pubmed: 26828865google scholar: lookup
      5. Cizauskas CA, Turner WC, Wagner B, Küsters M, Vance RE, Getz WM. Gastrointestinal helminths may affect host susceptibility to anthrax through seasonal immune trade-offs. BMC Ecol 2014 Nov 12;14:27.
        doi: 10.1186/s12898-014-0027-3pubmed: 25388877google scholar: lookup
      6. Bordin AI, Pillai SD, Brake C, Bagley KB, Bourquin JR, Coleman M, Oliveira FN, Mwangi W, McMurray DN, Love CC, Felippe MJ, Cohen ND. Immunogenicity of an electron beam inactivated Rhodococcus equi vaccine in neonatal foals. PLoS One 2014;9(8):e105367.
        doi: 10.1371/journal.pone.0105367pubmed: 25153708google scholar: lookup
      7. Lohmann KL, Lopez AM, Manning ST, Marques FJ, Brownlie R, Allen AL, Sangster AE, Mutwiri G, Gerdts V, Potter A, Townsend HG. Failure of a VapA/CpG oligodeoxynucleotide vaccine to protect foals against experimental Rhocococcus equi pneumonia despite induction of VapA-specific antibody and interferon-γ response. Can J Vet Res 2013 Jul;77(3):161-9.
        pubmed: 24101791
      8. Jacks S, Giguère S, Crawford PC, Castleman WL. Experimental infection of neonatal foals with Rhodococcus equi triggers adult-like gamma interferon induction. Clin Vaccine Immunol 2007 Jun;14(6):669-77.
        doi: 10.1128/CVI.00042-07pubmed: 17409222google scholar: lookup
      9. Jacks S, Giguère S, Prescott JF. In vivo expression of and cell-mediated immune responses to the plasmid-encoded virulence-associated proteins of Rhodococcus equi in foals. Clin Vaccine Immunol 2007 Apr;14(4):369-74.
        doi: 10.1128/CVI.00448-06pubmed: 17301216google scholar: lookup
      10. Flaminio MJ, Borges AS, Nydam DV, Horohov DW, Hecker R, Matychak MB. The effect of CpG-ODN on antigen presenting cells of the foal. J Immune Based Ther Vaccines 2007 Jan 25;5:1.
        doi: 10.1186/1476-8518-5-1pubmed: 17254326google scholar: lookup
      11. Horín P, Smola J, Matiasovic J, Vyskocil M, Lukeszová L, Tomanová K, Králík P, Glasnák V, Schröffelová D, Knoll A, Sedlinská M, Krenková L, Jahn P. Polymorphisms in equine immune response genes and their associations with infections. Mamm Genome 2004 Oct;15(10):843-50.
        doi: 10.1007/s00335-004-2356-6pubmed: 15520887google scholar: lookup
      12. Berghaus LJ, Venner M, Helbig H, Hildebrandt D, Hart K. The potential value of cytokine, cortisol and vitamin D profiles in foals from birth to weaning for respiratory disease prediction on a farm endemic for Rhodococcus equi pneumonia. Equine Vet J 2026 Mar;58(2):359-371.
        doi: 10.1111/evj.70093pubmed: 40923138google scholar: lookup
      13. da Silveira BP, Kahn SK, Legere RM, Bray JM, Cole-Pfeiffer HM, Golding MC, Cohen ND, Bordin AI. Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia. Sci Rep 2025 May 25;15(1):18156.
        doi: 10.1038/s41598-025-02060-5pubmed: 40415003google scholar: lookup
      14. Hu B, Gao S, Zhang H, Li Q, Li G, Zhang S, Xing Y, Huang Y, Han S, Tian Y, Zhang W, He H. Whole-genome sequencing and pathogenicity analysis of Rhodococcus equi isolated in horses. BMC Vet Res 2024 Aug 12;20(1):362.
        doi: 10.1186/s12917-024-04167-9pubmed: 39129003google scholar: lookup