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

Thomas Hopwood, Sarah Hall, Nicola Begley, Ruth Forman, Sheila Brown, Ryan Vonslow, Ben Saer, Matthew Little, Emma Murphy, Rebecca Hurst, David Ray, Andrew MacDonald, Andy Brass, David Bechtold, Julie Gibbs, Andrew Loudon, Kathryn Else

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Article number3782
JournalScientific Reports
Early online date28 Feb 2018
Publication statusPublished - 2018

Research Beacons, Institutes and Platforms

  • Manchester Institute for Collaborative Research on Ageing


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