Type I interferon licenses enhanced innate recognition and transcriptional responses to Franciscella tularensis live vaccine strain

Innate Immun. 2016 Jul;22(5):363-72. doi: 10.1177/1753425916650027. Epub 2016 May 26.

Abstract

The innate inflammatory response to Francisella tularensis (Ft) in macrophages is significantly governed by the expression of type I interferon (IFN). Previously, the proteolytic processing and maturation of pro-IL-1β protein was shown to depend upon type I IFN expression. We show in this report that paracrine type I IFN can profoundly enhance innate recognition and TLR-dependent transcriptional responses to Ft infection upstream of its role in inflammasome regulation in both primary human monocyte-derived macrophages and primary murine peritoneal macrophages but not murine bone marrow-derived macrophages. This type I IFN-enhanced response is synergistic with TLR2 transcriptional responses, partially TLR2-independent, but strictly MyD88-dependent.

Keywords: Francisella tularensis LVS; IFN-β; TLR2; macrophage; type I interferon.

MeSH terms

  • Animals
  • Francisella tularensis / immunology*
  • Humans
  • Immunity, Innate
  • Inflammasomes / metabolism
  • Interferon-beta / metabolism*
  • Interleukin-1beta / metabolism
  • Macrophages / physiology*
  • Macrophages, Peritoneal / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88 / metabolism*
  • Organ Specificity
  • RAW 264.7 Cells
  • Toll-Like Receptor 2 / metabolism
  • Transcription, Genetic
  • Tularemia

Substances

  • Inflammasomes
  • Interleukin-1beta
  • Myeloid Differentiation Factor 88
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Interferon-beta