{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T01:15:41Z","timestamp":1783559741965,"version":"3.55.0"},"reference-count":66,"publisher":"European Respiratory Society (ERS)","issue":"2","license":[{"start":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T00:00:00Z","timestamp":1557964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.ersjournals.com\/user-licence"}],"funder":[{"name":"South African National Research Foundation"},{"name":"South African Tuberculosis AIDS Training initiative"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2019,5,7]]},"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:p>Protective immunity against<jats:italic>Mycobacterium tuberculosis<\/jats:italic>is poorly understood. The role of interleukin (IL)-4, the archetypal T-helper type 2 (Th2) cytokine, in the immunopathogenesis of human tuberculosis remains unclear.<\/jats:p><jats:p>Blood and\/or bronchoalveolar lavage fluid (BAL) were obtained from participants with pulmonary tuberculosis (TB) (n=23) and presumed latent TB infection (LTBI) (n=22). Messenger RNA expression levels of interferon (IFN)-\u03b3, IL-4 and its splice variant IL-4\u03b42 were determined by real-time PCR. The effect of human recombinant (hr)IL-4 on mycobacterial survival\/containment (CFU\u00b7mL<jats:sup>\u22121<\/jats:sup>) was evaluated in<jats:italic>M. tuberculosis-<\/jats:italic>infected macrophages co-cultured with mycobacterial antigen-primed effector T-cells. Regulatory T-cell (Treg) and Th1 cytokine levels were evaluated using flow cytometry.<\/jats:p><jats:p>In blood, but not BAL, IL-4 mRNA levels (p=0.02) and the IL-4\/IFN-\u03b3 ratio (p=0.01) was higher in TB<jats:italic>versus<\/jats:italic>LTBI. hrIL-4 reduced mycobacterial containment in infected macrophages (p&lt;0.008) in a dose-dependent manner and was associated with an increase in Tregs (p&lt;0.001), but decreased CD4<jats:sup>+<\/jats:sup>Th1 cytokine levels (CD4<jats:sup>+<\/jats:sup>IFN-\u03b3<jats:sup>+<\/jats:sup>p&lt;0.001; CD4<jats:sup>+<\/jats:sup>TNF\u03b1<jats:sup>+<\/jats:sup>p=0.01). Blocking IL-4 significantly neutralised mycobacterial containment (p=0.03), CD4<jats:sup>+<\/jats:sup>IFN\u03b3<jats:sup>+<\/jats:sup>levels (p=0.03) and Treg expression (p=0.03).<\/jats:p><jats:p>IL-4 can subvert mycobacterial containment in human macrophages, probably<jats:italic>via<\/jats:italic>perturbations in Treg and Th1-linked pathways. 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