Abstract
Type I interferons (IFN-α and IFN-β) are important for protection against many viral infections, whereas type II interferon (IFN-γ) is essential for host defense against some bacterial and parasitic pathogens. Study of IFN responses in human leprosy revealed an inverse correlation between IFN-β and IFN-γ gene expression programs. IFN-γ and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in self-healing tuberculoid lesions and mediated antimicrobial activity against the pathogen Mycobacterium leprae in vitro. In contrast, IFN-β and its downstream genes, including interleukin-10 (IL-10), were induced in monocytes by M. leprae in vitro and preferentially expressed in disseminated and progressive lepromatous lesions. The IFN-γ-induced macrophage vitamin D-dependent antimicrobial peptide response was inhibited by IFN-β and by IL-10, suggesting that the differential production of IFNs contributes to protection versus pathogenesis in some human bacterial infections.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
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25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
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Antimicrobial Cationic Peptides / genetics
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Antimicrobial Cationic Peptides / metabolism
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Cathelicidins
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Humans
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Interferon-beta / genetics
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Interferon-beta / immunology*
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Interferon-beta / metabolism
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Interferon-gamma / genetics
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Interferon-gamma / immunology*
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Interferon-gamma / metabolism
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Interleukin-10 / genetics
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Interleukin-10 / metabolism
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Leprosy, Lepromatous / genetics
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Leprosy, Lepromatous / immunology*
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Leprosy, Lepromatous / metabolism
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Leprosy, Tuberculoid / genetics
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Leprosy, Tuberculoid / immunology*
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Leprosy, Tuberculoid / metabolism
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Microbial Viability
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Monocytes / immunology
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Monocytes / metabolism
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Mycobacterium leprae / immunology*
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Mycobacterium leprae / physiology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Calcitriol / genetics
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Receptors, Calcitriol / metabolism
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Transcriptome
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Tuberculosis / genetics
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Tuberculosis / immunology
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Up-Regulation
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beta-Defensins / genetics
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beta-Defensins / metabolism
Substances
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Antimicrobial Cationic Peptides
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DEFB4A protein, human
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RNA, Messenger
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Receptors, Calcitriol
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beta-Defensins
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Interleukin-10
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Interferon-beta
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Interferon-gamma
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25-Hydroxyvitamin D3 1-alpha-Hydroxylase
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Cathelicidins
Associated data
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GEO/GSE17763
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GEO/GSE43700