期刊
IMMUNOLOGY
卷 139, 期 1, 页码 121-128出版社
WILEY
DOI: 10.1111/imm.12062
关键词
antimicrobial peptides; autophagy; Mycobacteriumtuberculosis; T cells; vitamin D
类别
资金
- National Institutes of Health [NIH P50 - AR063020, RO1 AI022553, AR040312, AI047868, AI073539]
- Deutsche Forschungsgemeinschaft [FA849/1, SFB829]
- European Skin Research Foundation
- Ministry of Innovation, Science, Research and Technology of the German State of North Rhine-Westphalia
The ability of T cells to activate antimicrobial pathways in infected macrophages is essential to host defence against many intracellular pathogens. Here, we compared the ability of two T-cell-mediated mechanisms to trigger antimicrobial responses against Mycobacterium tuberculosis in humans, CD40 activation and the release of interferon- (IFN-). Given that IFN- activates a vitamin D-dependent antimicrobial response, we focused on induction of the key components of this pathway. We show that activation of human monocytes via CD40 ligand (CD40L) and IFN-, alone, and in combination, induces the CYP27b1-hydroxylase, responsible for the conversion of 25-hydroxyvitamin D (25D) to the bioactive 1,25-dihydroxyvitamin D (1,25D), and the vitamin D receptor (VDR). The activation of the vitamin D pathway by CD40L and IFN- results in up-regulated expression of the antimicrobial peptides, cathelicidin and DEFB4, as well as induction of autophagy. Finally, activation of monocytes via CD40L and IFN- results in an antimicrobial activity against intracellular M.tuberculosis. Our data suggest that at least two parallel T-cell-mediated mechanisms, CD40L and IFN-, activate the vitamin D-dependent antimicrobial pathway and trigger antimicrobial activity against intracellular M.tuberculosis, thereby contributing to human host defence against intracellular infection.
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