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CD40L and IFN-γ induce an antimicrobial response against M. tuberculosis in human monocytes.
MedLine Citation:
PMID:  23289765     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  JOURNAL ARTICLE     Date:  2013-1-5
Journal Detail:
Title:  Immunology     Volume:  -     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 The Authors. Immunology © 2013 Blackwell Publishing Ltd.
Affiliation:
Department of Dermatology, University of Cologne, Germany.
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