Type I interferon suppresses type II interferon–triggered human anti-mycobacterial responses

RMB Teles, TG Graeber, SR Krutzik, D Montoya… - Science, 2013 - science.org
RMB Teles, TG Graeber, SR Krutzik, D Montoya, M Schenk, DJ Lee, E Komisopoulou…
Science, 2013science.org
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 …
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.
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