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

Scientific Reports
Thomas W HopwoodKathryn J Else

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.

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Citations

Sep 19, 2019·Proceedings of the National Academy of Sciences of the United States of America·Chloé C NobisNicolas Cermakian
Dec 15, 2019·Immunology·Polly DowntonJulie E Gibbs
Jan 12, 2020·Current Allergy and Asthma Reports·Stephen N Waggoner
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Jan 11, 2020·Frontiers in Cellular and Infection Microbiology·Priscilla Carvalho CabralNicolas Cermakian
Dec 19, 2019·Genome Medicine·Filipa Rijo-Ferreira, Joseph S Takahashi
Aug 1, 2020·Frontiers in Immunology·Aïssatou Bailo DialloJean-Louis Mege
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Oct 10, 2020·Seminars in Immunopathology·John F Brooks, Lora V Hooper
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Nov 10, 2020·Journal of Biological Rhythms·Helene BorrmannXiaodong Zhuang
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Feb 14, 2020·Cell Host & Microbe·Kimberley F PriorSarah E Reece
Jan 14, 2022·Seminars in Immunopathology·Shannon L CoxRichard G Carroll

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Methods Mentioned

BETA
flow cytometry
RNA-Seq
Cytometric
FACS

Software Mentioned

FCAP Array
FastQC
Trimmomatic
Tophat
DESeq2
RontoTools
GraphPad Prism
R package topGO

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