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Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice

Veronika Lang, Sebastian Ferencik, Bharath Ananthasubramaniam, Achim Kramer, Bert Maier
doi: https://doi.org/10.1101/766519
Veronika Lang
1Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
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Sebastian Ferencik
1Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
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Bharath Ananthasubramaniam
1Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
2Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Germany
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Achim Kramer
1Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
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Bert Maier
1Laboratory of Chronobiology, Charité Universitätsmedizin Berlin, Germany
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  • For correspondence: bert.maier@charite.de
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Abstract

Local circadian clocks are active in most cells of our body. However, their impact on circadian physiology is still under debate. Mortality by endotoxic (LPS) shock is highly time-of-day dependent and local circadian immune function such as the cytokine burst after LPS challenge has been assumed to be causal for the large differences in survival. Here, we investigate the roles of light and myeloid clocks on mortality by endotoxic shock. Strikingly, mice in constant darkness (DD) show a three-fold increased susceptibility to LPS as compared to mice in light-dark conditions. Mortality by endotoxic shock as a function of circadian time is independent of light-dark cycles as well as myeloid CLOCK or BMAL1 as demonstrated in conditional knockout mice. Unexpectedly, despite the lack of a myeloid clock these mice still show rhythmic patterns of pro- and anti-inflammatory cytokines such as TNFα, MCP-1, IL-18 and IL-10 in peripheral blood as well as time-of-day and site dependent traffic of myeloid cells. We speculate that systemic time-cues are sufficient to orchestrate innate immune response to LPS by driving immune functions such as cell trafficking and cytokine expression.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • 1. Addition of supplemental data, table and figures

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 25, 2020.
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Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice
Veronika Lang, Sebastian Ferencik, Bharath Ananthasubramaniam, Achim Kramer, Bert Maier
bioRxiv 766519; doi: https://doi.org/10.1101/766519
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Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice
Veronika Lang, Sebastian Ferencik, Bharath Ananthasubramaniam, Achim Kramer, Bert Maier
bioRxiv 766519; doi: https://doi.org/10.1101/766519

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