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A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion

A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion
A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion
Six major lineages of Mycobacterium tuberculosis appear preferentially transmitted amongst distinct ethnic groups. We identified a deletion affecting Rv1519 in CH, a strain isolated from a large outbreak in Leicester U.K., that coincidentally defines the East African-Indian lineage matching a major ethnic group in this city. In broth media, CH grew less rapidly and was less acidic and H2O2-tolerant than reference sequenced strains (CDC1551 and H37Rv). Nevertheless, CH was not impaired in its ability to grow in human monocyte-derived macrophages. When compared with CDC1551 and H37Rv, CH induced less protective IL-12p40 and more antiinflammatory IL-10 and IL-6 gene transcription and secretion from monocyte-derived macrophages. It thus appears that CH compensates microbiological attenuation by skewing the innate response toward phagocyte deactivation. Complementation of Rv1519, but none of nine additional genes absent from CH compared with the type strain, H37Rv, reversed the capacity of CH to elicit antiinflammatory IL-10 production by macrophages. The Rv1519 polymorphism in M. tuberculosis confers an immune subverting phenotype that contributes to the persistence and outbreak potential of this lineage
0027-8424
15594-15598
Newton, S.M.
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Smith, R.J.
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Wilkinson, K.A.
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Nicol, M.P.
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Garton, N.J.
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Staples, K.J.
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Stewart, G.R.
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Wain, J.R.
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Martineau, A.R.
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Fandrich, S.
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Smallie, T.
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Foxwell, B.
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Al-Obaidi, A.
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Shafi, J.
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Rajakumar, K.
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Kampmann, B.
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Andrew, P.W.
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Ziegler-Heitbrock, L.
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Barer, M.R.
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Wilkinson, R.J.
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Newton, S.M.
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Smith, R.J.
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Wilkinson, K.A.
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Nicol, M.P.
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Garton, N.J.
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Staples, K.J.
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Stewart, G.R.
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Wain, J.R.
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Martineau, A.R.
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Fandrich, S.
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Smallie, T.
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Foxwell, B.
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Al-Obaidi, A.
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Shafi, J.
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Rajakumar, K.
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Kampmann, B.
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Andrew, P.W.
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Ziegler-Heitbrock, L.
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Barer, M.R.
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Wilkinson, R.J.
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Newton, S.M., Smith, R.J., Wilkinson, K.A., Nicol, M.P., Garton, N.J., Staples, K.J., Stewart, G.R., Wain, J.R., Martineau, A.R., Fandrich, S., Smallie, T., Foxwell, B., Al-Obaidi, A., Shafi, J., Rajakumar, K., Kampmann, B., Andrew, P.W., Ziegler-Heitbrock, L., Barer, M.R. and Wilkinson, R.J. (2006) A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion. Proceedings of the National Academy of Sciences, 103 (42), 15594-15598. (doi:10.1073/pnas.0604283103). (PMID:17028173)

Record type: Article

Abstract

Six major lineages of Mycobacterium tuberculosis appear preferentially transmitted amongst distinct ethnic groups. We identified a deletion affecting Rv1519 in CH, a strain isolated from a large outbreak in Leicester U.K., that coincidentally defines the East African-Indian lineage matching a major ethnic group in this city. In broth media, CH grew less rapidly and was less acidic and H2O2-tolerant than reference sequenced strains (CDC1551 and H37Rv). Nevertheless, CH was not impaired in its ability to grow in human monocyte-derived macrophages. When compared with CDC1551 and H37Rv, CH induced less protective IL-12p40 and more antiinflammatory IL-10 and IL-6 gene transcription and secretion from monocyte-derived macrophages. It thus appears that CH compensates microbiological attenuation by skewing the innate response toward phagocyte deactivation. Complementation of Rv1519, but none of nine additional genes absent from CH compared with the type strain, H37Rv, reversed the capacity of CH to elicit antiinflammatory IL-10 production by macrophages. The Rv1519 polymorphism in M. tuberculosis confers an immune subverting phenotype that contributes to the persistence and outbreak potential of this lineage

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Published date: 6 October 2006
Organisations: Faculty of Medicine

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Local EPrints ID: 374399
URI: http://eprints.soton.ac.uk/id/eprint/374399
ISSN: 0027-8424
PURE UUID: e3ad8ab4-4883-477f-bdea-cd29f2b23235
ORCID for K.J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

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Date deposited: 16 Feb 2015 11:30
Last modified: 17 Dec 2019 01:45

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Contributors

Author: S.M. Newton
Author: R.J. Smith
Author: K.A. Wilkinson
Author: M.P. Nicol
Author: N.J. Garton
Author: K.J. Staples ORCID iD
Author: G.R. Stewart
Author: J.R. Wain
Author: A.R. Martineau
Author: S. Fandrich
Author: T. Smallie
Author: B. Foxwell
Author: A. Al-Obaidi
Author: J. Shafi
Author: K. Rajakumar
Author: B. Kampmann
Author: P.W. Andrew
Author: L. Ziegler-Heitbrock
Author: M.R. Barer
Author: R.J. Wilkinson

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