Journal
SCIENCE
Volume 339, Issue 6126, Pages 1448-1453Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1233665
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Funding
- NIH [P50 AR063020, R01 AI022553, R01 AR040312, R01 AI047868, UL1TR000124]
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Type I interferons (IFN-alpha and IFN-beta) are important for protection against many viral infections, whereas type II interferon (IFN-gamma) is essential for host defense against some bacterial and parasitic pathogens. Study of IFN responses in human leprosy revealed an inverse correlation between IFN-beta and IFN-gamma gene expression programs. IFN-gamma 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-beta 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-gamma-induced macrophage vitamin D-dependent antimicrobial peptide response was inhibited by IFN-beta and by IL-10, suggesting that the differential production of IFNs contributes to protection versus pathogenesis in some human bacterial infections.
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