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Infection and immunity1999; 67(10); 5041-5047; doi: 10.1128/IAI.67.10.5041-5047.1999

Modulation of cytokine response of pneumonic foals by virulent Rhodococcus equi.

Abstract: The ability of Rhodococcus equi to induce pneumonia in foals depends on the presence of an 85- to 90-kb plasmid. In this study, we evaluated whether plasmid-encoded products mediate virulence by modulating the cytokine response of foals. Foals infected intrabronchially with a virulence plasmid-containing strain of R. equi had similar gamma interferon (IFN-gamma) and interleukin-12 (IL-12) p35 but significantly higher IL-1beta, IL-10, IL-12 p40, and tumor necrosis factor alpha (TNF-alpha) mRNA expression in lung tissue compared to foals infected with the plasmid-cured derivative. IFN-gamma mRNA expression levels in CD4+ T lymphocytes isolated from bronchial lymph nodes (BLN) were similar for the two groups of R. equi-infected foals on day 3 postinfection. However, on day 14, in association with pneumonia and marked multiplication of virulent R. equi but with complete clearance of the plasmid-cured derivative, IFN-gamma mRNA expression in BLN CD4+ T lymphocytes was significantly (P < 0.001) higher in foals infected with the plasmid-cured derivative. These results suggests an immunomodulating role for R. equi virulence plasmid-encoded products in downregulating IFN-gamma mRNA expression by CD4+ T lymphocytes.
Publication Date: 1999-09-25 PubMed ID: 10496876PubMed Central: PMC96851DOI: 10.1128/IAI.67.10.5041-5047.1999Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The article examines how the pneumonia-causing bacterium Rhodococcus equi influences the immune response in foals, specifically its ability to modulate cytokine response by encoding unique products on a specific 85-90kb plasmid.

Understanding the Research

  • The research primarily focused on Rhodococcus equi, a bacteria that can cause pneumonia in foals (baby horses). This bacterium is particularly virulent due to the presence of an 85 to 90-kb plasmid, a small, circular unit of DNA that is separate from the bacterial chromosome and carries genes that can confer survival advantages such as resistance to antibiotics.
  • The purpose of the study was to understand if plasmid-encoded products modulate or control the cytokine response in foals. Cytokines are essential cell signaling molecules that aid cell to cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection and trauma.

Testing Procedures and Observations

  • Foals were infected intrabronchially (directly into the bronchial tubes) with a strain of R. equi that carried the virulence plasmid. The cytokine response of this group of infected foals was compared with the response of foals infected with a derivative of R. equi that had been cured of the plasmid (i.e., the plasmid was removed;
  • Foals infected with the plasmid-carrying R. equi showed similar levels of gamma interferon (IFN-gamma) and interleukin-12 (IL-12) p35, but significantly increased levels of IL-1beta, IL-10, IL-12 p40, and tumor necrosis factor alpha (TNF-alpha). These are all different kinds of cytokines that elicit a diverse range of immune responses.
  • On the third day post-infection, IFN-gamma mRNA expression levels in the CD4+ T lymphocytes (a type of white blood cell essential for immune response) from bronchial lymph nodes were similar in both groups of foals.
  • By the 14th day post-infection, foals infected with the plasmid-cured derivative showed a significantly higher expression of IFN-gamma mRNA. This was despite the complete clearance of the plasmid-cured R. equi and the ongoing presence and multiplication of the virulent strain of the bacterium.

Conclusion and Implications

  • The results suggest that the products encoded by the R. equi virulence plasmid play a role in modulating the immune response by lowering the expression of IFN-gamma mRNA in CD4+ T lymphocytes.
  • The study generates a better understanding for future research into the virulence mechanisms of R. equi and the creation of potential therapies that could harness this modulatory capacity.

Cite This Article

APA
Giguère S, Wilkie BN, Prescott JF. (1999). Modulation of cytokine response of pneumonic foals by virulent Rhodococcus equi. Infect Immun, 67(10), 5041-5047. https://doi.org/10.1128/IAI.67.10.5041-5047.1999

Publication

ISSN: 0019-9567
NlmUniqueID: 0246127
Country: United States
Language: English
Volume: 67
Issue: 10
Pages: 5041-5047

Researcher Affiliations

Giguère, S
  • Department of Pathobiology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Wilkie, B N
    Prescott, J F

      MeSH Terms

      • Actinomycetales Infections / immunology
      • Actinomycetales Infections / veterinary
      • Animals
      • CD4-Positive T-Lymphocytes / immunology
      • Cytokines / biosynthesis
      • Cytokines / genetics
      • Horse Diseases / immunology
      • Horses
      • Pneumonia, Bacterial / veterinary
      • RNA, Messenger / analysis
      • Rhodococcus equi / pathogenicity
      • Virulence

      References

      This article includes 38 references
      1. 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
      2. Balson GA, Smith GD, Yager JA. Immunophenotypic analysis of foal bronchoalveolar lavage lymphocytes.. Vet Microbiol 1997 Jun 16;56(3-4):237-46.
        pubmed: 9226838doi: 10.1016/s0378-1135(97)00092-8google scholar: lookup
      3. Balson GA, Yager JA, Croy BA. SCID/beige mice in the study of immunity to Rhodococcus equi. In: Rossdale P D, Wade J F, editors. Equine infectious diseases. 6th ed. New Market, United Kingdom: R&W Publications; 1992. pp. 49–53.
      4. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.. Anal Biochem 1987 Apr;162(1):156-9.
        pubmed: 2440339doi: 10.1006/abio.1987.9999google scholar: lookup
      5. de la Peña-Moctezuma A, Prescott JF. Association with HeLa cells by Rhodococcus equi with and without the virulence plasmid.. Vet Microbiol 1995 Oct;46(4):383-92.
        pubmed: 8560735doi: 10.1016/0378-1135(95)00034-8google scholar: lookup
      6. 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.
      7. Giguère S, Hondalus MK, Yager JA, Darrah P, Mosser DM, Prescott JF. Role of the 85-kilobase plasmid and plasmid-encoded virulence-associated protein A in intracellular survival and virulence of Rhodococcus equi.. Infect Immun 1999 Jul;67(7):3548-57.
      8. Giguère S, Prescott JF. Cytokine induction in murine macrophages infected with virulent and avirulent Rhodococcus equi.. Infect Immun 1998 May;66(5):1848-54.
      9. Giguère S, Prescott JF. Quantitation of equine cytokine mRNA expression by reverse transcription-competitive polymerase chain reaction.. Vet Immunol Immunopathol 1999 Jan 4;67(1):1-15.
        pubmed: 9950350doi: 10.1016/s0165-2427(98)00212-8google scholar: lookup
      10. 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
      11. Hondalus MK, Diamond MS, Rosenthal LA, Springer TA, Mosser DM. The intracellular bacterium Rhodococcus equi requires Mac-1 to bind to mammalian cells.. Infect Immun 1993 Jul;61(7):2919-29.
      12. Jenne L, Kilwinski J, Scheffold W, Kern P. IL-5 expressed by CD4+ lymphocytes from Echinococcus multilocularis-infected patients.. Clin Exp Immunol 1997 Jul;109(1):90-7.
      13. 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.
      14. 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.
      15. 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.
      16. Kasuga-Aoki H, Takai S, Sasaki Y, Tsubaki S, Madarame H, Nakane A. Tumour necrosis factor and interferon-gamma are required in host resistance against virulent Rhodococcus equi infection in mice: cytokine production depends on the virulence levels of R. equi.. Immunology 1999 Jan;96(1):122-7.
      17. Lunn DP, Holmes MA, Duffus WP. Three monoclonal antibodies identifying antigens on all equine T lymphocytes, and two mutually exclusive T-lymphocyte subsets.. Immunology 1991 Oct;74(2):251-7.
        pmc: PMC1384601pubmed: 1748472
      18. Manyonda IT, Soltys AJ, Hay FC. A critical evaluation of the magnetic cell sorter and its use in the positive and negative selection of CD45RO+ cells.. J Immunol Methods 1992 Apr 27;149(1):1-10.
        pubmed: 1533866doi: 10.1016/s0022-1759(12)80042-1google scholar: lookup
      19. Marth T, Kelsall BL. Regulation of interleukin-12 by complement receptor 3 signaling.. J Exp Med 1997 Jun 2;185(11):1987-95.
        pmc: PMC2196332pubmed: 9166428doi: 10.1084/jem.185.11.1987google scholar: lookup
      20. Nakajima R, Brubaker RR. Association between virulence of Yersinia pestis and suppression of gamma interferon and tumor necrosis factor alpha.. Infect Immun 1993 Jan;61(1):23-31.
        pmc: PMC302683pubmed: 8418045doi: 10.1128/iai.61.1.23-31.1993google scholar: lookup
      21. Nordmann P, Ronco E, Nauciel C. Role of T-lymphocyte subsets in Rhodococcus equi infection.. Infect Immun 1992 Jul;60(7):2748-52.
      22. Powrie F, Bean D, Moore KW. Interleukin 10. In: Remick D G, Friedland J S, editors. Cytokines in health and disease. 2nd ed. New York, N.Y: Marcel Dekker Inc.; 1997. pp. 143–152.
      23. Prescott JF, Fernandez AS, Nicholson VM, Patterson MC, Yager JA, Viel L, Perkins G. Use of a virulence-associated protein based enzyme-linked immunosorbent assay for Rhodococcus equi serology in horses.. Equine Vet J 1996 Sep;28(5):344-9.
      24. 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
      25. Sekizaki T, Takai S, Egawa Y, Ikeda T, Ito H, Tsubaki S. Sequence of the Rhodococcus equi gene encoding the virulence-associated 15-17-kDa antigens.. Gene 1995 Mar 21;155(1):135-6.
        pubmed: 7698659doi: 10.1016/0378-1119(95)00009-ugoogle scholar: lookup
      26. Stanciu LA, Shute J, Holgate ST, Djukanović R. Production of IL-8 and IL-4 by positively and negatively selected CD4+ and CD8+ human T cells following a four-step cell separation method including magnetic cell sorting (MACS).. J Immunol Methods 1996 Jan 16;189(1):107-15.
        pubmed: 8576572doi: 10.1016/0022-1759(95)00240-5google scholar: lookup
      27. Steel RGD, Torrie JH. Principle and procedures of statistics. A biometrical approach. 2nd ed. New York, N.Y: McGraw-Hill; 1980.
      28. Sweeney RW, Jones DE, Habecker P, Scott P. Interferon-gamma and interleukin 4 gene expression in cows infected with Mycobacterium paratuberculosis.. Am J Vet Res 1998 Jul;59(7):842-7.
        pubmed: 9659548
      29. Swiderski CE, Klei TR, Horohov DW. Quantitative measurement of equine cytokine mRNA expression by polymerase chain reaction using target-specific standard curves.. J Immunol Methods 1999 Jan 1;222(1-2):155-69.
        pubmed: 10022382doi: 10.1016/s0022-1759(98)00193-8google scholar: lookup
      30. Takai S, Anzai T, Sasaki Y, Tsubaki S, Kamada M. Virulence of Rhodococcus equi isolated from lesions of infected foals. Bull Equine Res Inst 1993;30:9–14.
      31. Takai S, Imai Y, Fukunaga N, Uchida Y, Kamisawa K, Sasaki Y, Tsubaki S, Sekizaki T. Identification of virulence-associated antigens and plasmids in Rhodococcus equi from patients with AIDS.. J Infect Dis 1995 Nov;172(5):1306-11.
        pubmed: 7594668doi: 10.1093/infdis/172.5.1306google scholar: lookup
      32. 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.
      33. Takai S, Watanabe Y, Ikeda T, Ozawa T, Matsukura S, Tamada Y, Tsubaki S, Sekizaki T. Virulence-associated plasmids in Rhodococcus equi.. J Clin Microbiol 1993 Jul;31(7):1726-9.
      34. 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
      35. Trinchieri G, Gerosa F. Immunoregulation by interleukin-12.. J Leukoc Biol 1996 Apr;59(4):505-11.
        pubmed: 8613697doi: 10.1002/jlb.59.4.505google scholar: lookup
      36. Wada R, Kamada M, Anzai T, Nakanishi A, Kanemaru T, Takai S, Tsubaki S. Pathogenicity and virulence of Rhodococcus equi in foals following intratracheal challenge.. Vet Microbiol 1997 Jun 16;56(3-4):301-12.
        pubmed: 9226844doi: 10.1016/s0378-1135(97)00098-9google scholar: lookup
      37. 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
      38. Zhang M, Lin Y, Iyer DV, Gong J, Abrams JS, Barnes PF. T-cell cytokine responses in human infection with Mycobacterium tuberculosis.. Infect Immun 1995 Aug;63(8):3231-4.

      Citations

      This article has been cited 12 times.
      1. Xu Z, Hao X, Li M, Luo H. Rhodococcus equi-Derived Extracellular Vesicles Promoting Inflammatory Response in Macrophage through TLR2-NF-κB/MAPK Pathways.. Int J Mol Sci 2022 Aug 28;23(17).
        doi: 10.3390/ijms23179742pubmed: 36077142google scholar: lookup
      2. Vail KJ, da Silveira BP, Bell SL, Cohen ND, Bordin AI, Patrick KL, Watson RO. The opportunistic intracellular bacterial pathogen Rhodococcus equi elicits type I interferon by engaging cytosolic DNA sensing in macrophages.. PLoS Pathog 2021 Sep;17(9):e1009888.
        doi: 10.1371/journal.ppat.1009888pubmed: 34473814google scholar: lookup
      3. 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
      4. Giles C, Ndi O, Barton MD, Vanniasinkam T. An Adenoviral Vector Based Vaccine for Rhodococcus equi.. PLoS One 2016;11(3):e0152149.
        doi: 10.1371/journal.pone.0152149pubmed: 27008624google scholar: lookup
      5. Gurel V, Lambert K, Page AE, Loynachan AT, Huges K, Timoney JF, Fettinger M, Horohov DW, McMichael J. Streptolysin-O/antibiotics adjunct therapy modulates site-specific expression of extracellular matrix and inflammatory genes in lungs of Rhodococcus equi infected foals.. Vet Res Commun 2013 Jun;37(2):145-54.
        doi: 10.1007/s11259-013-9557-ypubmed: 23475766google scholar: lookup
      6. Prando C, Boisson-Dupuis S, Grant AV, Kong XF, Bustamante J, Feinberg J, Chapgier A, Rose Y, Jannière L, Rizzardi E, Zhang Q, Shanahan CM, Viollet L, Lyonnet S, Abel L, Ruga EM, Casanova JL. Paternal uniparental isodisomy of chromosome 6 causing a complex syndrome including complete IFN-gamma receptor 1 deficiency.. Am J Med Genet A 2010 Mar;152A(3):622-9.
        doi: 10.1002/ajmg.a.33291pubmed: 20186794google scholar: lookup
      7. Flaminio MJ, Nydam DV, Marquis H, Matychak MB, Giguère S. Foal monocyte-derived dendritic cells become activated upon Rhodococcus equi infection.. Clin Vaccine Immunol 2009 Feb;16(2):176-83.
        doi: 10.1128/CVI.00336-08pubmed: 19109450google scholar: lookup
      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. 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
      10. Hooper-McGrevy KE, Wilkie BN, Prescott JF. Immunoglobulin G subisotype responses of pneumonic and healthy, exposed foals and adult horses to Rhodococcus equi virulence-associated proteins.. Clin Diagn Lab Immunol 2003 May;10(3):345-51.
      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 Mar;10(2):208-15.
      12. 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.