| CD40L and IFN-γ induce an antimicrobial response against M. tuberculosis in human monocytes. | |
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MedLine Citation:
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PMID: 23289765 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The ability of T cells to activate antimicrobial pathways in infected macrophages is essential to host defense 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 IFN-γ. Given that IFN-γ 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 CD40L and IFN-γ, 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/or IFN-γ results in upregulated expression of the antimicrobial peptides, cathelicidin and DEFB4, as well as induction of autophagy. Finally, activation of monocytes via CD40L and/or IFN-γ results in an antimicrobial activity against intracellular M. tuberculosis. Our data suggest that at least two parallel T cell-mediated mechanisms, CD40L and IFN-γ, activate the vitamin D-dependent antimicrobial pathway and trigger antimicrobial activity against intracellular M. tuberculosis, thereby contributing to human host defense against intracellular infection. © 2013 The Authors. Immunology © 2013 Blackwell Publishing Ltd. |
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Authors:
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Georgiana M Klug-Micu; Steffen Stenger; Andrea Sommer; Philip T Liu; Stephan R Krutzik; Robert L Modlin; Mario Fabri |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-5 |
Journal Detail:
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Title: Immunology Volume: - ISSN: 1365-2567 ISO Abbreviation: Immunology Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0374672 Medline TA: Immunology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2013 The Authors. Immunology © 2013 Blackwell Publishing Ltd. |
Affiliation:
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Department of Dermatology, University of Cologne, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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