期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 52, 页码 22593-22598出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1011624108
关键词
innate immune response; interferon-gamma; interleukin-4; Mycobacterium tuberculosis
资金
- Wenner-Gren Foundation
- National Institutes of Health [AI 022553, AI 047868, AI 073539]
We investigated the mechanisms by which T-cell cytokines are able to influence the Toll-like receptor (TLR)-induced, vitamin D-dependent antimicrobial pathway in human monocytes. T-cell cytokines differentially influenced TLR2/1-induced expression of the antimicrobial peptides cathelicidin and DEFB4, being up-regulated by IFN-gamma, down-regulated by IL-4, and unaffected by IL-17. The Th1 cytokine IFN-gamma up-regulated TLR2/1 induction of 25-hydroxyvitamin D-1 alpha-hydroxylase (i.e., CYP27B1), leading to enhanced bioconversion of 25-hydroxyvitamin D-3 (25D(3)) to its active metabolite 1,25D(3). In contrast, the Th2 cytokine IL-4, by itself and in combination with the TLR2/1 ligand, induced catabolism of 25D(3) to the inactive metabolite 24,25D(3), and was dependent on expression of vitamin D-24-hydroxylase (i.e., CYP24A1). Therefore, the ability of T-cell cytokines to differentially control monocyte vitamin D metabolism represents a mechanism by which cell-mediated immune responses can regulate innate immune mechanisms to defend against microbial pathogens.
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