The circadian regulator BMAL1 programmes responses to parasitic worm infection via a dendritic cell clock
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 T H...
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Published in | Scientific reports Vol. 8; no. 1; pp. 3782 - 13 |
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Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
28.02.2018
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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 T
H
2 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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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-018-22021-5 |