Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice

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...

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Autores principales:	Veronika Lang, Sebastian Ferencik, Bharath Ananthasubramaniam, Achim Kramer, Bert Maier
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	circadian rhythm sepsis macrophages Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b242c8964a0c4b2fa6702dd21b7e54b1
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spelling	oai:doaj.org-article:b242c8964a0c4b2fa6702dd21b7e54b12021-11-17T14:21:23ZSusceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice10.7554/eLife.624692050-084Xe62469https://doaj.org/article/b242c8964a0c4b2fa6702dd21b7e54b12021-10-01T00:00:00Zhttps://elifesciences.org/articles/62469https://doaj.org/toc/2050-084XLocal 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 threefold 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.Veronika LangSebastian FerencikBharath AnanthasubramaniamAchim KramerBert MaiereLife Sciences Publications Ltdarticlecircadian rhythmsepsismacrophagesMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	circadian rhythm sepsis macrophages Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	circadian rhythm sepsis macrophages Medicine R Science Q Biology (General) QH301-705.5 Veronika Lang Sebastian Ferencik Bharath Ananthasubramaniam Achim Kramer Bert Maier Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice
description	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 threefold 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.
format	article
author	Veronika Lang Sebastian Ferencik Bharath Ananthasubramaniam Achim Kramer Bert Maier
author_facet	Veronika Lang Sebastian Ferencik Bharath Ananthasubramaniam Achim Kramer Bert Maier
author_sort	Veronika Lang
title	Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice
title_short	Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice
title_full	Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice
title_fullStr	Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice
title_full_unstemmed	Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice
title_sort	susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/b242c8964a0c4b2fa6702dd21b7e54b1
work_keys_str_mv	AT veronikalang susceptibilityrhythmtobacterialendotoxininmyeloidclockknockoutmice AT sebastianferencik susceptibilityrhythmtobacterialendotoxininmyeloidclockknockoutmice AT bharathananthasubramaniam susceptibilityrhythmtobacterialendotoxininmyeloidclockknockoutmice AT achimkramer susceptibilityrhythmtobacterialendotoxininmyeloidclockknockoutmice AT bertmaier susceptibilityrhythmtobacterialendotoxininmyeloidclockknockoutmice
_version_	1718425503641108480

Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice

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