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Suppressor of cytokine signaling-3 is affected in T-cells from tuberculosis TB patients
Department of Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany; Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
Research Institute for the Biology of Farm Animals, Genetics and Biometry, Dummerstorf, Germany.ORCID iD: 0000-0002-7173-5579
Department of Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
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2011 (English)In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 17, no 9, p. 1323-31Article in journal (Refereed) Published
Abstract [en]

T-cells and T-cell-derived cytokines are crucial mediators of protection against Mycobacterium tuberculosis infection, but these factors are insufficient as biomarkers for disease susceptibility. In order to define T-cell molecules involved in tuberculosis (TB), we compared gene expression profiles of T-cells from patients with active TB, healthy donors with latent M. tuberculosis infection (LTBIs) and non-infected healthy donors (NIDs) by microarray analysis. Pathway-focused analyses identified a prevalent subset of candidate genes involved in the Janus kinase (JAK)-signal transducer and activator of transcription signalling pathway, including those encoding suppressor of cytokine signalling (SOCS) molecules, in the subset of protection-associated genes. Differential expression was verified by quantitative PCR analysis for the cytokine-inducible SH2-containing protein (CISH), SOCS3, JAK3, interleukin-2 receptor α-chain (IL2RA), and the proto-oncogene serine/threonine protein kinase (PIM1). Classification analyses revealed that this set of molecules was able to discriminate efficiently between T-cells from TB patients and those from LTBIs, and, notably, to achieve optimal discrimination between LTBIs and NIDs. Further characterization by quantitative PCR revealed highly variable candidate gene expression in CD4(+) and CD8(+) T-cells from TB patients and only minor differences between CD4(+) and CD8(+) T-cell subpopulations. These results point to a role of cytokine receptor signalling regulation in T-cells in susceptibility to TB.

Place, publisher, year, edition, pages
Malden, USA: Wiley-Blackwell, 2011. Vol. 17, no 9, p. 1323-31
Keywords [en]
Latent Mycobacterium tuberculosis infection, suppressor of cytokine signalling, T-cell subpopulations, T-cells, tuberculosis
National Category
Biochemistry Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-40735DOI: 10.1111/j.1469-0691.2010.03326.xISI: 000294125000006PubMedID: 20673263Scopus ID: 2-s2.0-80051890565OAI: oai:DiVA.org:oru-40735DiVA, id: diva2:778567
Available from: 2015-01-11 Created: 2015-01-11 Last updated: 2025-02-20Bibliographically approved

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