The circadian regulator BMAL1 programmes responses to parasitic worm infection via a dendritic cell clock

Sci Rep. 2018 Feb 28;8(1):3782. doi: 10.1038/s41598-018-22021-5.

Abstract

Resistance to the intestinal parasitic helminth Trichuris muris requires T-helper 2 (TH2) cellular and associated IgG1 responses, with expulsion typically taking up to 4 weeks in mice. Here, we show that the time-of-day of the initial infection affects efficiency of worm expulsion, with strong TH2 bias and early expulsion in morning-infected mice. Conversely, mice infected at the start of the night show delayed resistance to infection, and this is associated with feeding-driven metabolic cues, such that feeding restriction to the day-time in normally nocturnal-feeding mice disrupts parasitic expulsion kinetics. We deleted the circadian regulator BMAL1 in antigen-presenting dendritic cells (DCs) in vivo and found a loss of time-of-day dependency of helminth expulsion. RNAseq analyses revealed that IL-12 responses to worm antigen by circadian-synchronised DCs were dependent on BMAL1. Therefore, we find that circadian machinery in DCs contributes to the TH1/TH2 balance, and that environmental, or genetic perturbation of the DC clock results in altered parasite expulsion kinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / physiology*
  • Animals
  • Cells, Cultured
  • Circadian Rhythm*
  • Dendritic Cells / immunology*
  • Dendritic Cells / parasitology
  • Lymph Nodes / immunology*
  • Lymph Nodes / parasitology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / immunology
  • T-Lymphocytes / parasitology
  • Th2 Cells / immunology*
  • Th2 Cells / parasitology
  • Trichuriasis / immunology*
  • Trichuriasis / parasitology
  • Trichuris / pathogenicity*

Substances

  • ARNTL Transcription Factors
  • Bmal1 protein, mouse