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Constitutive STAT3 phosphorylation and IL-6/IL-10 co-expression are associated with impaired T-cell function in tuberculosis patients

Cellular & Molecular Immunologyvolume 16pages275287 (2019) | Download Citation



T-cells critically contribute to protection against Mycobacterium tuberculosis infection, and impaired T-cell responses can lead to disease progression. Pro-inflammatory and immunosuppressive cytokines affect T-cells, and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function. Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases. We characterized blood samples from tuberculosis patients (n=28) and healthy contacts (n=28) from Ghana for M. tuberculosis-specific T-cell responses, constitutive cytokine production, and SOCS3 and pSTAT3 expression. Lentiviral modulation of primary CD4+ T-cells was performed to determine the effects of SOCS3 on T-cell functions. T-cells from tuberculosis patients expressed higher levels of IL-10 and IL-6 and lower levels of T helper type (TH)17 cytokines after M. tuberculosis-specific stimulation compared to healthy contacts. In addition, tuberculosis patients had higher IL-10 and IL-6 levels in the supernatants of non-stimulated immune cells and plasma samples compared to healthy contacts. Notably, aberrant cytokine expression was accompanied by high constitutive pSTAT3 levels and SOCS3 expression in T-cells. Multivariate analysis identified an IL-6/IL-10 co-expression-based principal component in tuberculosis patients that correlated with high pSTAT3 levels. SOCS3 contributed to a regulatory component, and tuberculosis patients with high SOCS3 expression showed decreased TH1 cytokine expression and impaired IL-2-induced STAT5 phosphorylation. SOCS3 over-expression in primary CD4+ T-cells confirmed the SOCS3 inhibitory function on IL-2-induced STAT5 phosphorylation. We conclude that constitutive pSTAT3 and high SOCS3 expression are influential factors that indicate impaired T-cell functions in tuberculosis patients.

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We would like to thank all study participants, study nurses, and physicians who made this study possible. This study was supported by the German Research Foundation (DFG, JA 1479/5-1) to N Nausch, E. Owusu-Dabo, and M. Jacobsen. K. Harling were supported by the ‘Hedwig und Waldemar Hort Stipendienstiftung’. E. Adankwah and M. Jacobsen were supported by the Manchot graduate school ‘Molecules of Infection (MOI)-3’.

Author information


  1. Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children’s Hospital, 40225, Duesseldorf, Germany

    • Kirstin Harling
    • , Ernest Adankwah
    • , Alptekin Güler
    • , Ertan Mayatepek
    • , Norman Nausch
    •  & Marc Jacobsen
  2. Kumasi Centre for collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana

    • Anthony Afum-Adjei Awuah
    • , Louis Adu-Amoah
    •  & Ellis Owusu-Dabo
  3. School of Public Health, College of Health Sciences, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana

    • Anthony Afum-Adjei Awuah
    •  & Ellis Owusu-Dabo


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Correspondence to Marc Jacobsen.

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