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Inhibition of Abl\u2010tyrosine kinases has evolved as a new concept for the treatment of CML and other malignant diseases. Due to the multiple immune\u2010modulatory pathways controlled by tyrosine kinases, treatment with tyrosine kinase inhibitors (TKIs) will not only affect the biology of malignant cells but also modulate physiological immune functions. To understand the effects of TKIs on host defense against intracellular bacteria, we investigated the immunological impact of the dual Abl\/Src TKI dasatinib on the cellular immune response to <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>). Our results demonstrate that dasatinib impaired proliferation, cytokine release (IFN\u2010\u03b3, TNF\u2010\u03b1, GM\u2010CSF), expression of granulysin and degranulation of cytotoxic effector molecules of human <jats:italic>Mtb<\/jats:italic>\u2010specific T\u2010lymphocytes by inhibition of lymphocyte\u2010specific protein tyrosine kinase (Lck) phosphorylation. Despite this profound inhibition of T\u2010cell function, dasatinib suppressed growth of virulent <jats:italic>Mtb<\/jats:italic> in human macrophages co\u2010cultured with autologous <jats:italic>Mtb<\/jats:italic>\u2010specific T\u2010cells (49\u00b115%). Functional analysis suggested that growth inhibition is due to dasatinib\u2010triggered lysosomal acidification in <jats:italic>Mtb<\/jats:italic>\u2010infected macrophages. These results highlight the significance of innate immune responses, i.e. acidification of lysosomes, which control the multiplication of intracellular bacteria despite the lack of efficient T\u2010cell support.<\/jats:p>","DOI":"10.1002\/eji.201847656","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T13:15:16Z","timestamp":1537622116000},"page":"1892-1903","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The tyrosine kinase inhibitor dasatinib reduces the growth of intracellular <i>Mycobacterium tuberculosis<\/i> despite impairing T\u2010cell function"],"prefix":"10.1002","volume":"48","author":[{"given":"Stephanie","family":"Wehrstedt","sequence":"first","affiliation":[{"name":"Institute for Medical Microbiology and Hygiene University Hospital Ulm  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