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Home / Equine Research Bank / Vet Sci / IgG Subtype Response against Virulence-Associated Protein A ...
Veterinary sciences2024; 11(9); 422; doi: 10.3390/vetsci11090422

IgG Subtype Response against Virulence-Associated Protein A in Foals Naturally Infected with Rhodococcus equi.

Abstract: is an intracellular bacterium that causes suppurative pneumonia in foals. T-helper (Th) 1 cells play an important role in the protective response against . In mice and humans, the directionality of IgG switching reflects the polarization of Th-cell responses, but this has not been fully elucidated in horses. In this 4-year study, we classified -infected foals into surviving and non-surviving group and investigated differences in IgG subclass response to virulence-associated protein A, the main virulence factor of , between the groups. IgGa, IgGb, and IgG(T) titers were significantly higher in the non-surviving group compared with the surviving group. The titers of IgGa and IgG(T), IgGb and IgG(T), and IgGa and IgGb, respectively, were positively correlated, and the IgG(T)/IgGb ratio in the non-surviving group was significantly higher than that in the surviving group. The IgG(T) titer tended to increase more than the IgGa and IgGb titers in the non-surviving group compared with the surviving group. Our findings suggest that the IgG(T) bias in IgG subclass responses reflects the immune status, which exacerbates infection.
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Publication Date: 2024-09-09 PubMed ID: 39330801PubMed Central: PMC11435873DOI: 10.3390/vetsci11090422Google Scholar: Lookup
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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.

Overview

  • This study investigated the immune response, specifically IgG antibody subtypes, in foals naturally infected with the bacterium Rhodococcus equi, which causes pneumonia.
  • The research examined differences in IgG subclass antibodies against a key bacterial virulence protein between foals that survived infection and those that did not, aiming to understand how immune responses correlate with disease outcome.

Background

  • Rhodococcus equi is an intracellular bacterial pathogen responsible for suppurative (pus-forming) pneumonia in young horses (foals).
  • Effective immunity against this pathogen is complex and is strongly influenced by T-helper 1 (Th1) cell-mediated immune responses.
  • IgG antibodies have different subclasses, and their patterns can indicate whether the immune response is leaning more towards a Th1 or Th2 profile, as seen in mice and humans.
  • In horses, the relationship between these IgG subclasses and protective immunity to R. equi had not been clearly defined before this study.

Study Design and Methods

  • The study was conducted over four years with naturally infected foals.
  • Foals infected with R. equi were sorted into two groups: those that survived the infection and those that did not survive.
  • Researchers measured levels (titers) of different IgG subclasses targeting the virulence-associated protein A (VapA), a major virulence factor of R. equi.
  • Specifically, they focused on three subclasses: IgGa, IgGb, and IgG(T), the equine IgG subtype thought to be involved in Th1-type immunity.

Key Findings

  • Titers of IgGa, IgGb, and IgG(T) antibodies were significantly higher in foals that did not survive compared to those that did survive.
  • Positive correlations were observed between IgGa and IgG(T), IgGb and IgG(T), and IgGa and IgGb, indicating these subclasses increased together to some extent.
  • The ratio of IgG(T) to IgGb was significantly greater in the non-surviving group, suggesting an increased bias toward IgG(T) subtype in those foals.
  • IgG(T) titers increased disproportionately more than IgGa and IgGb in the non-surviving foals, implying a skewed immune response.

Interpretation and Implications

  • The increased IgG(T) response relative to other IgG subclasses in non-surviving foals indicates a particular type of immune response associated with worse outcomes.
  • Contrary to what might be expected if IgG(T) reflected protective Th1 immunity, the bias toward IgG(T) suggests an immune status that actually exacerbates the disease or fails to protect the foal effectively.
  • This finding highlights that the mere presence of a certain IgG subclass is not always protective and may reflect immune dysregulation or ineffective immune polarization in naturally infected foals.
  • Understanding these IgG subclass dynamics could inform future vaccine design or immune therapies by targeting a more balanced or effective immune response against R. equi.

Conclusion

  • This research clarifies how IgG subclass responses against VapA differ between foals that survive or succumb to R. equi pneumonia.
  • The bias towards IgG(T) in non-surviving foals suggests that this immune profile is associated with disease severity rather than protection.
  • These insights contribute to a better understanding of equine immune responses to R. equi and could aid in improving clinical management and prevention strategies for affected foals.

Cite This Article

APA
Mizuguchi Y, Tsuzuki N, Ebana MD, Suzuki Y, Kakuda T. (2024). IgG Subtype Response against Virulence-Associated Protein A in Foals Naturally Infected with Rhodococcus equi. Vet Sci, 11(9), 422. https://doi.org/10.3390/vetsci11090422

Publication

Veterinary sciences
ISSN: 2306-7381
NlmUniqueID: 101680127
Country: Switzerland
Language: English
Volume: 11
Issue: 9
PII: 422

Researcher Affiliations

Mizuguchi, Yuya
  • Mitsuishi Animal Medical Center, Hokkaido 059-3105, Japan.
Tsuzuki, Nao
  • Department of Veterinary Medicine, Rakuno Gakuen University, Hokkaido 069-8501, Japan.
Ebana, Marina Dee
  • Laboratory of Animal Hygiene, Faculty of Veterinary Medicine, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan.
Suzuki, Yasunori
  • Laboratory of Animal Hygiene, Faculty of Veterinary Medicine, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan.
Kakuda, Tsutomu
  • Laboratory of Animal Hygiene, Faculty of Veterinary Medicine, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan.

Conflict of Interest Statement

The authors declare no conflicts of interest.

References

This article includes 36 references
  1. Prescott JF. R. equi: An animal and human pathogen.. Clin. Microbiol. Rev. 1991;4:20–34.
    doi: 10.1128/CMR.4.1.20pmc: PMC358176pubmed: 2004346google scholar: lookup
  2. Takai S. Epidemiology of Rhodococcus equi infections: A review.. Vet. Microbiol. 1997;56:167–176.
    doi: 10.1016/S0378-1135(97)00085-0pubmed: 9226831google scholar: lookup
  3. Giguère S, Cohen ND, Chaffin MK, Hines SA, Hondalus MK, Prescott JF, Slovis NM. Rhodococcus equi: Clinical manifestations, virulence, and immunity.. J. Vet. Intern. Med. 2011;25:1221–1230.
    doi: 10.1111/j.1939-1676.2011.00804.xpubmed: 22092609google scholar: lookup
  4. Petry S, Sévin C, Fleury MA, Duquesne F, Foucher N, Laugier C, Henry-Amar M, Tapprest J. Differential distribution of vapA-positive Rhodococcus equi in affected and unaffected horse-breeding farms.. Vet. Rec. 2017;181:145.
    doi: 10.1136/vr.104088pubmed: 28642343google scholar: lookup
  5. Venner M, Kerth R, Klug E. Evaluation of tulathromycin in the treatment of pulmonary abscesses in foals.. Vet. J. 2007;174:418–421.
    doi: 10.1016/j.tvjl.2006.08.016pubmed: 17045497google scholar: lookup
  6. Fernandez-Mora E, Polidori M, Lührmann A, Schaible UE, Haas A. Maturation of Rhodococcus equi-containing vacuoles is arrested after completion of the early endosome stage.. Traffic. 2005;6:635–653.
    doi: 10.1111/j.1600-0854.2005.00304.xpubmed: 15998320google scholar: lookup
  7. Haubenthal T, Hansen P, Krämer I, Gindt M, Jünger-Leif A, Utermöhlen O, Haas A. Specific preadaptations of Rhodococcus equi cooperate with its Virulence-associated protein A during macrophage infection.. Mol. Microbiol. 2023;119:285–301.
    doi: 10.1111/mmi.15026pubmed: 36627747google scholar: lookup
  8. von Bargen K, Scraba M, Krämer I, Ketterer M, Nehls C, Krokowski S, Repnik U, Wittlich M, Maaser A, Zapka P. Virulence-associated protein A from Rhodococcus equi is an intercompartmental pH-neutralising virulence factor.. Cell. Microbiol. 2019;21:e12958.
    pubmed: 30251327
  9. 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;64:1126–1132.
    doi: 10.1128/iai.64.4.1126-1132.1996pmc: PMC173893pubmed: 8606068google scholar: lookup
  10. Kanaly ST, Hines SA, Palmer GH. Failure of pulmonary clearance of Rhodococcus equi infection in CD4+ T-lymphocyte-deficient transgenic mice.. Infect. Immun. 1993;61:4929–4932.
    doi: 10.1128/iai.61.11.4929-4932.1993pmc: PMC281259pubmed: 8104903google scholar: lookup
  11. Hines SA, Stone DM, Hines MT, Alperin DC, Knowles DP, Norton LK, Hamilton MJ, Davis WC, McGuire TC. Clearance of virulent but not avirulent Rhodococcus equi from the lungs of adult horses is associated with intracytoplasmic gamma interferon production by CD4+ and CD8+ T lymphocytes.. Clin. Diagn. Lab. Immunol. 2003;10:208–215.
    pmc: PMC150533pubmed: 12626444
  12. Hines SA, Kanaly ST, Byrne BA, Palmer GH. Immunity to Rhodococcus equi.. Vet. Microbiol. 1997;56:177–185.
    doi: 10.1016/S0378-1135(97)00086-2pubmed: 9226832google scholar: lookup
  13. Harris SP, Hines MT, Mealey RH, Alperin DC, Hines SA. Early development of cytotoxic T lymphocytes in neonatal foals following oral inoculation with Rhodococcus equi.. Vet. Immunol. Immunopathol. 2011;141:312–326.
    doi: 10.1016/j.vetimm.2011.03.015pmc: PMC3345954pubmed: 21481947google scholar: lookup
  14. Patton KM, McGuire TC, Hines MT, Mealey RH, Hines SA. Rhodococcus equi-specific cytotoxic T lymphocytes in immune horses and development in asymptomatic foals.. Infect. Immun. 2005;73:2083–2093.
    doi: 10.1128/IAI.73.4.2083-2093.2005pmc: PMC1087435pubmed: 15784549google scholar: lookup
  15. Patton KM, McGuire TC, Fraser DG, Hines SA. Rhodococcus equi-infected macrophages are recognized and killed by CD8+ T lymphocytes in a major histocompatibility complex class I-unrestricted fashion.. Infect. Immun. 2004;72:7073–7083.
    doi: 10.1128/IAI.72.12.7073-7083.2004pmc: PMC529141pubmed: 15557631google scholar: lookup
  16. Olatunde A.C., Hale J.S., Lamb T.J. Cytokine-skewed Tfh cells: Functional consequences for B cell help. Trends Immunol. 2021;42:536–550. doi: 10.1016/j.it.2021.04.006.
    doi: 10.1016/j.it.2021.04.006pmc: PMC9107098pubmed: 33972167google scholar: lookup
  17. Eisenbarth S.C., Baumjohann D., Craft J., Fazilleau N., Ma C.S., Tangye S.G., Vinuesa C.G., Linterman M.A. CD4+ T cells that help B cells—A proposal for uniform nomenclature. Trends Immunol. 2021;42:658–669. doi: 10.1016/j.it.2021.06.003.
    doi: 10.1016/j.it.2021.06.003pmc: PMC8324560pubmed: 34244056google scholar: lookup
  18. Abbas A.K., Murphy K.M., Sher A. Functional diversity of helper T lymphocytes. Nature. 1996;383:787–793. doi: 10.1038/383787a0.
    doi: 10.1038/383787a0pubmed: 8893001google scholar: lookup
  19. Romagnani S. The Th1/Th2 paradigm. Immunol Today. 1997;18:263–266. doi: 10.1016/S0167-5699(97)80019-9.
    doi: 10.1016/S0167-5699(97)80019-9pubmed: 9190109google scholar: lookup
  20. Kaufmann S.H. Immunity to intracellular bacteria. Annu Rev Immunol. 1993;11:129–163. doi: 10.1146/annurev.iy.11.040193.001021.
    doi: 10.1146/annurev.iy.11.040193.001021pubmed: 8476559google scholar: lookup
  21. Urban J.F., Jr., Noben-Trauth N., Donaldson D.D., Madden K.B., Morris S.C., Collins M., Finkelman F.D. IL-13, IL-4Ralpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity. 1998;8:255–264. doi: 10.1016/S1074-7613(00)80477-X.
    doi: 10.1016/S1074-7613(00)80477-Xpubmed: 9492006google scholar: lookup
  22. Toellner K.M., Luther S.A., Sze D.M., Choy R.K., Taylor D.R., MacLennan I.C., Acha-Orbea H. T helper 1 (Th1) and Th2 characteristics start to develop during T cell priming and are associated with an immediate ability to induce immunoglobulin class switching. J. Exp. Med. 1998;187:1193–1204. doi: 10.1084/jem.187.8.1193.
    doi: 10.1084/jem.187.8.1193pmc: PMC2212236pubmed: 9547331google scholar: lookup
  23. Foote C.E., Love D.N., Gilkerson J.R., Rota J., Trevor-Jones P., Ruitenberg K.M., Wellington J.E., Whalley J.M. Serum antibody responses to equine herpesvirus 1 glycoprotein D in horses, pregnant mares and young foals. Vet. Immunol. Immunopathol. 2005;105:47–57. doi: 10.1016/j.vetimm.2004.12.012.
    doi: 10.1016/j.vetimm.2004.12.012pubmed: 15797474google scholar: lookup
  24. Swiderski C.E., Klei T.R., Folsom R.W., Pourciau S.S., Chapman A., Chapman M.R., Moore R.M., McClure J.R., Taylor H.W., Horohov D.W. Vaccination against Strongylus vulgaris in ponies: Comparison of the humoral and cytokine responses of vaccinates and nonvaccinates. Adv. Vet. Med. 1999;41:389–404.
    pubmed: 9890030
  25. Jacks S., Giguère S., Crawford P.C., Castleman W.L. Experimental infection of neonatal foals with Rhodococcus equi triggers adult-like gamma interferon induction. Clin. Vaccine. Immunol. 2007;14:669–677. doi: 10.1128/CVI.00042-07.
    doi: 10.1128/CVI.00042-07pmc: PMC1951072pubmed: 17409222google scholar: lookup
  26. Lewis M.J., Wagner B., Woof J.M. The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies. Mol. Immunol. 2008;45:818–827. doi: 10.1016/j.molimm.2007.06.158.
    doi: 10.1016/j.molimm.2007.06.158pmc: PMC2075531pubmed: 17669496google scholar: lookup
  27. Sanz M.G., Villarino N., Ferreira-Oliveira A., Horohov D.W. VapA-specific IgG and IgG subclasses responses after natural infection and experimental challenge of foals with Rhodococcus equi. Vet. Immunol. Immunopathol. 2015;164:10–15. doi: 10.1016/j.vetimm.2015.01.004.
    doi: 10.1016/j.vetimm.2015.01.004pubmed: 25681111google scholar: lookup
  28. Sangkanjanavanich N., Kawai M., Kakuda T., Takai S. Rescue of an intracellular avirulent Rhodococcus equi replication defect by the extracellular addition of virulence-associated protein A. J. Vet. Med. Sci. 2017;79:1323–1326. doi: 10.1292/jvms.17-0350.
    doi: 10.1292/jvms.17-0350pmc: PMC5573816pubmed: 28690290google scholar: lookup
  29. Akobeng A.K. Understanding diagnostic tests 3: Receiver operating characteristic curves. Acta Paediatr. 2007;96:644–647. doi: 10.1111/j.1651-2227.2006.00178.x.
    doi: 10.1111/j.1651-2227.2006.00178.xpubmed: 17376185google scholar: lookup
  30. Giguère S., Cohen N.D., Chaffin M.K., Slovis N.M., Hondalus M.K., Hines S.A., Prescott J.F. Diagnosis, treatment, control, and prevention of infections caused by Rhodococcus equi in foals. J. Vet. Intern. Med. 2011;25:1209–1220. doi: 10.1111/j.1939-1676.2011.00835.x.
    doi: 10.1111/j.1939-1676.2011.00835.xpubmed: 22092608google scholar: lookup
  31. Lopez A.M., Hines M.T., Palmer G.H., Alperin D.C., Hines S.A. Identification of pulmonary T-lymphocyte and serum antibody isotype responses associated with protection against Rhodococcus equi. Clin. Diagn. Lab. Immunol. 2002;9:1270–1276.
    pmc: PMC130094pubmed: 12414760
  32. Kelso A. Th1 and Th2 subsets: Paradigms lost? Immunol. Today. 1995;16:374–379. doi: 10.1016/0167-5699(95)80004-2.
    doi: 10.1016/0167-5699(95)80004-2pubmed: 7546192google scholar: lookup
  33. Rogozynski N.P., Dixon B. The Th1/Th2 paradigm: A misrepresentation of helper T cell plasticity. Immunol. Lett. 2024;268:106870. doi: 10.1016/j.imlet.2024.106870.
    doi: 10.1016/j.imlet.2024.106870pubmed: 38788801google scholar: lookup
  34. Jacks S., Giguère S. Effects of inoculum size on cell-mediated and humoral immune responses of foals experimentally infected with Rhodococcus equi: A pilot study. Vet Immunol Immunopathol. 2010;133:282–286. doi: 10.1016/j.vetimm.2009.08.004.
    doi: 10.1016/j.vetimm.2009.08.004pubmed: 19720402google scholar: lookup
  35. Álvarez-Narváez S., Huber L., Giguère S., Hart K.A., Berghaus R.D., Sanchez S., Cohen N.D. Epidemiology and molecular basis of multidrug resistance in Rhodococcus equi. Microbiol. Mol. Biol. Rev. 2021;85:e00011-21. doi: 10.1128/MMBR.00011-21.
    doi: 10.1128/MMBR.00011-21pmc: PMC8139527pubmed: 33853933google scholar: lookup
  36. Venner M., Rödiger A., Laemmer M., Giguère S. Failure of antimicrobial therapy to accelerate spontaneous healing of subclinical pulmonary abscesses on a farm with endemic infections caused by Rhodococcus equi. Vet. J. 2012;192:293–298. doi: 10.1016/j.tvjl.2011.07.004.
    doi: 10.1016/j.tvjl.2011.07.004pubmed: 21924651google scholar: lookup

Citations

This article has been cited 1 times.
  1. Reguzova A, Haug V, Müller M, Fandrich M, Dulovic A, Amann R. Heterologous ORFV-Ad26 vaccination broadens antibody breadth and amplifies cellular immunity against SARS-CoV-2 spike.. Front Immunol 2025;16:1715442.
    doi: 10.3389/fimmu.2025.1715442pubmed: 41341596google scholar: lookup
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