Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41598-018-22021-5
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Funding
- Medical Research Council (MRC) [MR/N022661/1]
- Wellcome Trust [091815]
- BBSRC
- Biotechnology and Biological Sciences Research Council Case (BBSRC)
- Flow cytometry, Histology and the Genomic Technologies Core Facilities at the University of Manchester
- BBSRC [BB/L000954/1] Funding Source: UKRI
- MRC [MR/M008908/1, MR/P023576/1, MR/N022661/1, MR/L018640/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [1497765, BB/L000954/1] Funding Source: researchfish
- Medical Research Council [MR/P023576/1, MR/L018640/1, MR/N022661/1, MR/M008908/1] Funding Source: researchfish
- Versus Arthritis [20629] Funding Source: researchfish
- Wellcome Trust [107851/Z/15/Z] Funding Source: researchfish
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Resistance to the intestinal parasitic helminth Trichuris muris requires T-helper 2 (T(H)2) 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 T(H)1/T(H)2 balance, and that environmental, or genetic perturbation of the DC clock results in altered parasite expulsion kinetics.
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