دورية أكاديمية
IL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity
| العنوان: | IL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity |
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| المؤلفون: | Judith Schick, Meltem Altunay, Matthew Lacorcia, Nathalie Marschner, Stefanie Westermann, Julia Schluckebier, Christoph Schubart, Barbara Bodendorfer, Dennis Christensen, Christian Alexander, Stefan Wirtz, David Voehringer, Clarissa Prazeres da Costa, Roland Lang |
| المصدر: | eLife, Vol 12 (2023) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | co-infection, Th cell differentiation, Nippostrongylus brasiliensis, Schistosoma mansoni, mycobacterial cord factor, C-type lectin receptors, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | 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 Mycobacterium bovis 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 Nippostrongylus brasiliensis in monocytes. To determine the impact of helminth infection on MINCLE-dependent immune responses, we vaccinated mice with a recombinant protein together with the MINCLE ligand trehalose-6,6-dibehenate (TDB) as adjuvant. Concurrent infection with N. brasiliensis or with Schistosoma mansoni promoted T cell-derived IL-4 production and suppressed Th1/Th17 differentiation in the spleen. In contrast, helminth infection did not reduce Th1/Th17 induction by TDB in draining peripheral lymph nodes, where IL-4 levels were unaltered. Upon use of the TLR4-dependent adjuvant G3D6A, N. brasiliensis infection impaired selectively the induction of splenic antigen-specific Th1 but not of Th17 cells. Inhibition of MINCLE-dependent Th1/Th17 responses in mice infected with N. brasiliensis was dependent on IL-4/IL-13. Thus, helminth infection attenuated the Th17 response to MINCLE-dependent immunization in an organ- and adjuvant-specific manner via the Th2 cytokines IL-4/IL-13. Taken together, our results demonstrate downregulation of MINCLE expression on monocytes and macrophages by IL-4 as a possible mechanism of thwarted Th17 vaccination responses by underlying helminth infection. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/72923Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.72923 |
| الوصول الحر: | https://doaj.org/article/5ae7b59983a44ed9bd8dcf86dc279bbfTest |
| رقم الانضمام: | edsdoj.5ae7b59983a44ed9bd8dcf86dc279bbf |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.72923 |