The role of Interleukin-7 signalling in active tuberculosis

Previous investigations indicated that Interleukin-7 (IL-7) enhanced the M. tuberculosis specific T cell response. Activation of the T cell receptor (TCR) by M. tuberculosis specific proteins is promoted by IL-7, leading to enhanced cytokine e.g. IFN-? expression. This circumstance raises a number of questions. In terms of diagnostics, it is intriguing to characterize the capacity of IL-7 to increase the specificity of IFN-? release assays (IGRAs). Initial studies indicate a role of IL-7 availability during tuberculosis disease. In this study, we aim at identifying molecules that regulate IL-7 signalling and how M. tuberculosis infection and disease may interfere with IL-7 promoted T cell response. A possible target is the JAK/STAT pathway. Binding of IL-7 to its receptor leads to JAK-mediated phosphorylation of STAT5 and STAT3, which then dimerize and migrate to the cell nucleus to act as transcription factors. Activated STAT molecules are in turn targeted by so-called suppressors of cytokine signalling (SOCS) molecules, which regulate JAK/STAT signalling. Increased expression of SOCS family members, SOCS3 and CISH in T cells from tuberculosis patients have been described (Jacobsen et al. Clinical Microbiology and Infection, 2011).

This study was performed in cooperation with Prof. E. Owusu-Dabo and Dr. A. Afum-Awuah Adjei at the Kumasi Center for Collaborative Research in Tropical Medicine (KCCR) in Kumasi, Ghana. The project was supervised by Dr. N. Nausch. The project was funded by the German Leprosy and Tuberculosis Relief Association (DAHW) and the Deutsche Forschungsgemeinschaft (DFG). K. Harling received additional support from the Hedwig und Waldemar Hort Stipendienstiftung.

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