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PMID: 23449998 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Science (New York, N.Y.) ·Vol. 339 ·No. 6126 ·2013-03-22 ·Pages 1448-53

Teles RM, Graeber TG, Krutzik SR, Montoya D, Schenk M, Lee DJ, Komisopoulou E, Kelly-Scumpia K, Chun R, Iyer SS, Sarno EN, Rea TH, Hewison M, Adams JS, Popper SJ, Relman DA, Stenger S, Bloom BR, Cheng G, Modlin RL

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.

MeSH Terms
25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics,metabolism Antimicrobial Cationic Peptides/genetics,metabolism Humans Interferon-beta/genetics,immunology,metabolism Interferon-gamma/genetics,immunology,metabolism Interleukin-10/genetics,metabolism Leprosy, Lepromatous/genetics,immunology,metabolism Leprosy, Tuberculoid/genetics,immunology,metabolism Microbial Viability Monocytes/immunology,metabolism Mycobacterium leprae/immunology,physiology RNA, Messenger/genetics,metabolism Receptors, Calcitriol/genetics,metabolism Transcriptome Tuberculosis/genetics,immunology Up-Regulation beta-Defensins/genetics,metabolism
Chemicals
Antimicrobial Cationic Peptides DEFB4A protein, human RNA, Messenger Receptors, Calcitriol beta-Defensins Interleukin-10 ropocamptide Interferon-beta Interferon-gamma 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Teles Rosane M B
Division of Dermatology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
Graeber Thomas G
Krutzik Stephan R
Montoya Dennis
Schenk Mirjam
Lee Delphine J
Komisopoulou Evangelia
Kelly-Scumpia Kindra
Chun Rene
Iyer Shankar S
Sarno Euzenir N
Rea Thomas H
Hewison Martin
Adams John S
Popper Stephen J
Relman David A
Stenger Steffen
Bloom Barry R
Cheng Genhong
Modlin Robert L
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1233665
Published
2013-03-22
Epub
2013-00-28
Pages
1448-53
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3653587
Subset
IM
Grants
NCATS NIH HHS · UL1TR000124 · United States
NIAID NIH HHS · R01 AI022553 · United States
NIAID NIH HHS · R01 AI047868 · United States
NCATS NIH HHS · UL1 TR000124 · United States
NCI NIH HHS · T32 CA009120 · United States
NIAID NIH HHS · R01 AI082575 · United States
NIAMS NIH HHS · P50 AR063020 · United States
NIAMS NIH HHS · R01 AR059126 · United States
NIAID NIH HHS · R37 AI047868 · United States
NIAID NIH HHS · R01 AI056154 · United States
NIAMS NIH HHS · R01 AR040312 · United States
Databases
GEO
GSE17763, GSE43700
Corrections
CommentIn
PMID: 23601100
External Links
PubMed source DOI: 10.1126/science.1233665 PMC Full Text View journal details
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