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

Research output: Contribution to journalArticle

Authors

  • 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
  • John S Adams
  • Stephen J Popper
  • David A Relman
  • Steffen Stenger
  • Barry R Bloom
  • Genhong Cheng
  • Robert L Modlin

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)1448-53
Number of pages6
JournalScience
Volume339
Issue number6126
Publication statusPublished - 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