Immune responses to the enduring hypoxic response antigen Rv0188 are preferentially detected in Mycobacterium bovis infected cattle with low pathology

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dc.contributor.authorJones, Gareth Jen_ZA
dc.contributor.authorPirson, Chrisen_ZA
dc.contributor.authorGideon, Hannah Pen_ZA
dc.contributor.authorWilkinson, Katalin Aen_ZA
dc.contributor.authorSherman, David Ren_ZA
dc.contributor.authorWilkinson, Robert Jen_ZA
dc.contributor.authorHewinson, R Glynen_ZA
dc.contributor.authorVordermeier, H Martinen_ZA
dc.date.accessioned2016-01-11T06:53:31Z
dc.date.available2016-01-11T06:53:31Z
dc.date.issued2011en_ZA
dc.description.abstractThe DosR regulon and the Enduring Hypoxic Response (EHR) define a group of M. tuberculosis genes that are specifically induced in bacilli exposed in vitro to conditions thought to mimic the environment encountered by Mycobacteria during latent infection. Although well described in humans, latent mycobacterial infection in cattle remains poorly understood. Thus, the aim of this study was to identify antigens that may potentially disclose cattle with latent M. bovis infection. To this end, we initially screened 57 pools of overlapping peptides representing 4 DosR regulon and 29 EHR antigens for their ability to stimulate an immune response in whole blood from TB-reactor cattle using IFN-γ and IL-2 as readouts. All 4 DosR regulon proteins were poorly recognized (maximum responder frequency of 10%). For the EHR antigens, both IFN-γ and IL-2 revealed similar response hierarchies, with responder frequencies ranging from 54% down to 3% depending on the given EHR antigen. Furthermore, these results demonstrated that responses in the infected cattle were largely IFN-γ biased. To support the concept for their role in latency, we evaluated if EHR antigen responses were associated with lower pathology. The EHR antigen Rv0188 was recognised predominantly in animals presenting with low pathology scores, whereas responses to ESAT-6/CFP-10 or the other EHR antigens tested were prevalent across the pathology spectrum. However, when we determined the production of additional cytokines induced by the M. bovis antigens PPD-B or ESAT-6/CFP-10, we detected significantly greater PPD-B-induced production of the pro-inflammatory cytokine IL-1β in animals recognizing Rv0188 (i.e. those with limited or no pathology). Thus, these results are consistent with the idea that responses to Rv0188 may identify a subset of animals at early stages of infection or in which disease progression may be limited.en_ZA
dc.identifier.apacitationJones, G. J., Pirson, C., Gideon, H. P., Wilkinson, K. A., Sherman, D. R., Wilkinson, R. J., ... Vordermeier, H. M. (2011). Immune responses to the enduring hypoxic response antigen Rv0188 are preferentially detected in Mycobacterium bovis infected cattle with low pathology. <i>PLoS One</i>, http://hdl.handle.net/11427/16282en_ZA
dc.identifier.chicagocitationJones, Gareth J, Chris Pirson, Hannah P Gideon, Katalin A Wilkinson, David R Sherman, Robert J Wilkinson, R Glyn Hewinson, and H Martin Vordermeier "Immune responses to the enduring hypoxic response antigen Rv0188 are preferentially detected in Mycobacterium bovis infected cattle with low pathology." <i>PLoS One</i> (2011) http://hdl.handle.net/11427/16282en_ZA
dc.identifier.citationJones, G. J., Pirson, C., Gideon, H. P., Wilkinson, K. A., Sherman, D. R., Wilkinson, R. J., ... & Vordermeier, H. M. (2011). Immune responses to the enduring hypoxic response antigen Rv0188 are preferentially detected in Mycobacterium bovis infected cattle with low pathology. PloS one, 6(6), e21371. doi:10.1371/journal.pone.0021371en_ZA
dc.identifier.ris TY - Journal Article AU - Jones, Gareth J AU - Pirson, Chris AU - Gideon, Hannah P AU - Wilkinson, Katalin A AU - Sherman, David R AU - Wilkinson, Robert J AU - Hewinson, R Glyn AU - Vordermeier, H Martin AB - The DosR regulon and the Enduring Hypoxic Response (EHR) define a group of M. tuberculosis genes that are specifically induced in bacilli exposed in vitro to conditions thought to mimic the environment encountered by Mycobacteria during latent infection. Although well described in humans, latent mycobacterial infection in cattle remains poorly understood. Thus, the aim of this study was to identify antigens that may potentially disclose cattle with latent M. bovis infection. To this end, we initially screened 57 pools of overlapping peptides representing 4 DosR regulon and 29 EHR antigens for their ability to stimulate an immune response in whole blood from TB-reactor cattle using IFN-γ and IL-2 as readouts. All 4 DosR regulon proteins were poorly recognized (maximum responder frequency of 10%). For the EHR antigens, both IFN-γ and IL-2 revealed similar response hierarchies, with responder frequencies ranging from 54% down to 3% depending on the given EHR antigen. Furthermore, these results demonstrated that responses in the infected cattle were largely IFN-γ biased. To support the concept for their role in latency, we evaluated if EHR antigen responses were associated with lower pathology. The EHR antigen Rv0188 was recognised predominantly in animals presenting with low pathology scores, whereas responses to ESAT-6/CFP-10 or the other EHR antigens tested were prevalent across the pathology spectrum. However, when we determined the production of additional cytokines induced by the M. bovis antigens PPD-B or ESAT-6/CFP-10, we detected significantly greater PPD-B-induced production of the pro-inflammatory cytokine IL-1β in animals recognizing Rv0188 (i.e. those with limited or no pathology). Thus, these results are consistent with the idea that responses to Rv0188 may identify a subset of animals at early stages of infection or in which disease progression may be limited. DA - 2011 DB - OpenUCT DO - 10.1371/journal.pone.0021371 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - Immune responses to the enduring hypoxic response antigen Rv0188 are preferentially detected in Mycobacterium bovis infected cattle with low pathology TI - Immune responses to the enduring hypoxic response antigen Rv0188 are preferentially detected in Mycobacterium bovis infected cattle with low pathology UR - http://hdl.handle.net/11427/16282 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16282
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0021371
dc.identifier.vancouvercitationJones GJ, Pirson C, Gideon HP, Wilkinson KA, Sherman DR, Wilkinson RJ, et al. Immune responses to the enduring hypoxic response antigen Rv0188 are preferentially detected in Mycobacterium bovis infected cattle with low pathology. PLoS One. 2011; http://hdl.handle.net/11427/16282.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2011 Jones et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherCattleen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherAntigensen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherMycobacterium bovisen_ZA
dc.subject.otherRegulonsen_ZA
dc.subject.otherTuberculosisen_ZA
dc.titleImmune responses to the enduring hypoxic response antigen Rv0188 are preferentially detected in Mycobacterium bovis infected cattle with low pathologyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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