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

Rosane M B Teles; Thomas G Graeber; Stephan R Krutzik; Dennis Montoya; Mirjam Schenk; Delphine J Lee; Evangelia Komisopoulou; Kindra Kelly-Scumpia; Rene Chun; Shankar S Iyer; Euzenir N Sarno; Thomas H Rea; Martin Hewison; John S Adams; Stephen J Popper; David A Relman; Steffen Stenger; Barry R Bloom; Genhong Cheng; Robert L Modlin

doi:10.1126/science.1233665

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

Rosane M B Teles, Thomas G Graeber, Stephan R Krutzik, Dennis Montoya, Mirjam Schenk, Delphine J Lee, Evangelia Komisopoulou, Kindra Kelly-Scumpia, Rene Chun, Shankar S Iyer, Euzenir N Sarno, Thomas H Rea, Martin Hewison, John S Adams, Stephen J Popper, David A Relman, Steffen Stenger, Barry R Bloom, Genhong Cheng, Robert L Modlin

Metabolism and Systems Research

Research output: Contribution to journal › Article › peer-review

257 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1448-53
Number of pages	6
Journal	Science
Volume	339
Issue number	6126
DOIs	https://doi.org/10.1126/science.1233665
Publication status	Published - 22 Mar 2013

Keywords

25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Antimicrobial Cationic Peptides
Humans
Interferon-beta
Interferon-gamma
Interleukin-10
Leprosy, Lepromatous
Leprosy, Tuberculoid
Microbial Viability
Monocytes
Mycobacterium leprae
RNA, Messenger
Receptors, Calcitriol
Transcriptome
Tuberculosis
Up-Regulation
beta-Defensins

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1126/science.1233665

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Teles, R. M. B., Graeber, T. G., Krutzik, S. R., Montoya, D., Schenk, M., Lee, D. J., Komisopoulou, E., Kelly-Scumpia, K., Chun, R., Iyer, S. S., Sarno, E. N., Rea, T. H., Hewison, M., Adams, J. S., Popper, S. J., Relman, D. A., Stenger, S., Bloom, B. R., Cheng, G., & Modlin, R. L. (2013). Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses. Science, 339(6126), 1448-53. https://doi.org/10.1126/science.1233665

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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.",

keywords = "25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Antimicrobial Cationic Peptides, Humans, Interferon-beta, Interferon-gamma, Interleukin-10, Leprosy, Lepromatous, Leprosy, Tuberculoid, Microbial Viability, Monocytes, Mycobacterium leprae, RNA, Messenger, Receptors, Calcitriol, Transcriptome, Tuberculosis, Up-Regulation, beta-Defensins",

author = "Teles, {Rosane M B} and Graeber, {Thomas G} and Krutzik, {Stephan R} and Dennis Montoya and Mirjam Schenk and Lee, {Delphine J} and Evangelia Komisopoulou and Kindra Kelly-Scumpia and Rene Chun and Iyer, {Shankar S} and Sarno, {Euzenir N} and Rea, {Thomas H} and Martin Hewison and Adams, {John S} and Popper, {Stephen J} and Relman, {David A} and Steffen Stenger and Bloom, {Barry R} and Genhong Cheng and Modlin, {Robert L}",

year = "2013",

month = mar,

day = "22",

doi = "10.1126/science.1233665",

language = "English",

volume = "339",

pages = "1448--53",

journal = "Science",

issn = "0036-8075",

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Teles, RMB, 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 2013, 'Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses', Science, vol. 339, no. 6126, pp. 1448-53. https://doi.org/10.1126/science.1233665

TY - JOUR

T1 - Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses

AU - Teles, Rosane M B

AU - Graeber, Thomas G

AU - Krutzik, Stephan R

AU - Montoya, Dennis

AU - Schenk, Mirjam

AU - Lee, Delphine J

AU - Komisopoulou, Evangelia

AU - Kelly-Scumpia, Kindra

AU - Chun, Rene

AU - Iyer, Shankar S

AU - Sarno, Euzenir N

AU - Rea, Thomas H

AU - Hewison, Martin

AU - Adams, John S

AU - Popper, Stephen J

AU - Relman, David A

AU - Stenger, Steffen

AU - Bloom, Barry R

AU - Cheng, Genhong

AU - Modlin, Robert L

PY - 2013/3/22

Y1 - 2013/3/22

N2 - 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.

AB - 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.

KW - 25-Hydroxyvitamin D3 1-alpha-Hydroxylase

KW - Antimicrobial Cationic Peptides

KW - Humans

KW - Interferon-beta

KW - Interferon-gamma

KW - Interleukin-10

KW - Leprosy, Lepromatous

KW - Leprosy, Tuberculoid

KW - Microbial Viability

KW - Monocytes

KW - Mycobacterium leprae

KW - RNA, Messenger

KW - Receptors, Calcitriol

KW - Transcriptome

KW - Tuberculosis

KW - Up-Regulation

KW - beta-Defensins

U2 - 10.1126/science.1233665

DO - 10.1126/science.1233665

M3 - Article

C2 - 23449998

SN - 0036-8075

VL - 339

SP - 1448

EP - 1453

JO - Science

JF - Science

IS - 6126

ER -

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

Abstract

Keywords

UN SDGs

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