University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Immune Responses to the Enduring Hypoxic Response Antigen Rv0188 Are Preferentially Detected in Mycobacterium bovis Infected Cattle with Low Pathology

Jones, GJ, Pirson, C, Gideon, HP, Wilkinson, KA, Sherman, DR, Wilkinson, RJ, Hewinson, RG and Vordermeier, HM (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), ARTN e.

[img]
Preview
Text
Immune responses to the enduring hypoxic response antigen Rv0188 are preferentially detected in Mycobacterium bovis infected cattle with low pathology..pdf - ["content_typename_Published version (Publisher's proof or final PDF)" not defined]
Available under License : See the attached licence file.

Download (232kB) | Preview
[img]
Preview
PDF (licence)
SRI_deposit_agreement.pdf
Available under License : See the attached licence file.

Download (33kB) | Preview

Abstract

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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Microbial and Cellular Sciences
Authors :
AuthorsEmailORCID
Jones, GJUNSPECIFIEDUNSPECIFIED
Pirson, CUNSPECIFIEDUNSPECIFIED
Gideon, HPUNSPECIFIEDUNSPECIFIED
Wilkinson, KAUNSPECIFIEDUNSPECIFIED
Sherman, DRUNSPECIFIEDUNSPECIFIED
Wilkinson, RJUNSPECIFIEDUNSPECIFIED
Hewinson, RGUNSPECIFIEDUNSPECIFIED
Vordermeier, HMUNSPECIFIEDUNSPECIFIED
Date : 21 June 2011
Identification Number : 10.1371/journal.pone.0021371
Uncontrolled Keywords : Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, MULTIDISCIPLINARY SCIENCES, BCG VACCINATION, TUBERCULOSIS INFECTION, ALPHA-CRYSTALLIN, LATENCY, REGULON, REACTIVATION, RECOGNITION, INSIGHTS, BIOLOGY, PROTEIN
Related URLs :
Additional Information : This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Depositing User : Symplectic Elements
Date Deposited : 19 Aug 2015 12:46
Last Modified : 19 Aug 2015 12:46
URI: http://epubs.surrey.ac.uk/id/eprint/808108

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800