biostudies-literatureSchick JDeutsche Forschungsgemeinschafte72923https://www.ebi.ac.uk/biostudies/studies/S-EPMC9908076biostudies-literatureUnknown12The myeloid C-type lectin receptor (CLR) MINCLE senses the mycobacterial cell wall component trehalose-6,6'-dimycolate (TDM). Recently, we found that IL-4 downregulates MINCLE expression in macrophages. IL-4 is a hallmark cytokine in helminth infections, which appear to increase the risk for mycobacterial infection and active tuberculosis. Here, we investigated functional consequences of IL-4 and helminth infection on MINCLE-driven macrophage activation and Th1/Th17 adjuvanticity. IL-4 inhibited MINCLE and cytokine induction after macrophage infection with <i>Mycobacterium bovis</i> bacille Calmette-Guerin (BCG). Infection of mice with BCG upregulated MINCLE on myeloid cells, which was inhibited by IL-4 plasmid injection and by infection with the nematode <i>Nippostrongylus brasiliensis</ieLifeIL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity.PMC9908076LA 1262/8-1CO 1469/16-1CDC 1181_A02Schubart CWestermann SLacorcia MBodendorfer BAltunay MMarschner NAlexander Cda Costa CPLang RSchick JChristensen DSchluckebier JWirtz SVoehringer DfalseIL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity.The myeloid C-type lectin receptor (CLR) MINCLE senses the mycobacterial cell wall component trehalose-6,6'-dimycolate (TDM). Recently, we found that IL-4 downregulates MINCLE expression in macrophages. IL-4 is a hallmark cytokine in helminth infections, which appear to increase the risk for mycobacterial infection and active tuberculosis. Here, we investigated functional consequences of IL-4 and helminth infection on MINCLE-driven macrophage activation and Th1/Th17 adjuvanticity. IL-4 inhibited MINCLE and cytokine induction after macrophage infection with <i>Mycobacterium bovis</i> bacille Calmette-Guerin (BCG). Infection of mice with BCG upregulated MINCLE on myeloid cells, which was inhibited by IL-4 plasmid injection and by infection with the nematode <i>Nippostrongylus brasiliensis</i2023-01-01T00:00:00Z2023 Feb2025-04-04T18:43:32.965Z2025-04-04T18:43:32.965ZS-EPMC99080763675343410.7554/eLife.72923