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Science 339 (6126): 1448-1453

Copyright © 2013 by the American Association for the Advancement of Science

Type I Interferon Suppresses Type II Interferon–Triggered Human Anti-Mycobacterial Responses

Rosane M. B. Teles,1 Thomas G. Graeber,4 Stephan R. Krutzik,1 Dennis Montoya,1 Mirjam Schenk,1 Delphine J. Lee,5 Evangelia Komisopoulou,4 Kindra Kelly-Scumpia,1 Rene Chun,3 Shankar S. Iyer,2 Euzenir N. Sarno,6 Thomas H. Rea,7 Martin Hewison,3 John S. Adams,3 Stephen J. Popper,8 David A. Relman,8,9 Steffen Stenger,10 Barry R. Bloom,11 Genhong Cheng,2 Robert L. Modlin1,2,*

Abstract: Type I interferons (IFN-α and IFN-β) 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-β 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-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-{gamma}–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.

1 Division of Dermatology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
2 Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
3 UCLA/Orthopedic Hospital Department of Orthopedic Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
4 Crump Institute for Molecular Imaging, Institute for Molecular Medicine, Johnson Comprehensive Cancer Center, California NanoSystems Institute, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
5 Department of Translational Immunology, John Wayne Cancer Institute, Santa Monica, CA, USA.
6 Department of Mycobacteriosis, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.
7 Department of Dermatology, University of Southern California School of Medicine, Los Angeles, CA 90033, USA.
8 Department of Microbiology and Immunology and Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
9 Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
10 Institute for Medical Microbiology and Hygiene, University Hospital of Ulm, Germany.
11 Harvard School of Public Health, Boston, MA 02115, USA.

* Corresponding author. E-mail: rmodlin{at}mednet.ucla.edu


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