title: Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses.
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.
authors: Division of Dermatology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
authors: Rosane M B
authors: RM
authors: Teles
authors: Thomas G
authors: TG
authors: Graeber
authors: Stephan R
authors: SR
authors: Krutzik
authors: Dennis
authors: D
authors: Montoya
authors: Mirjam
authors: M
authors: Schenk
authors: Delphine J
authors: DJ
authors: Lee
authors: Evangelia
authors: E
authors: Komisopoulou
authors: Kindra
authors: K
authors: Kelly-Scumpia
authors: Rene
authors: R
authors: Chun
authors: Shankar S
authors: SS
authors: Iyer
authors: Euzenir N
authors: EN
authors: Sarno
authors: Thomas H
authors: TH
authors: Rea
authors: Martin
authors: M
authors: Hewison
authors: John S
authors: JS
authors: Adams
authors: Stephen J
authors: SJ
authors: Popper
authors: David A
authors: DA
authors: Relman
authors: Steffen
authors: S
authors: Stenger
authors: Barry R
authors: BR
authors: Bloom
authors: Genhong
authors: G
authors: Cheng
authors: Robert L
authors: RL
authors: Modlin
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015440:Leprosy, Lepromatous / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015441:Leprosy, Tuberculoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050296:Microbial Viability; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009166:Mycobacterium leprae / Q000276:immunology* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; C106641:DEFB4A protein, human; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D023083:beta-Defensins; D016753:Interleukin-10; D016899:Interferon-beta; D007371:Interferon-gamma; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D054804:Cathelicidins