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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/62469 |
| _version_ | 1828382741393047552 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T04:37:45Z |
| format | Article |
| id | doaj.art-b242c8964a0c4b2fa6702dd21b7e54b1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:37:45Z |
| publishDate | 2021-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b242c8964a0c4b2fa6702dd21b7e54b12022-12-22T02:01:58ZengeLife Sciences Publications LtdeLife2050-084X2021-10-011010.7554/eLife.62469Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout miceVeronika Lang0Sebastian Ferencik1Bharath Ananthasubramaniam2https://orcid.org/0000-0003-4467-1546Achim Kramer3Bert Maier4https://orcid.org/0000-0002-5254-008XLaboratory of Chronobiology, Charité Universitätsmedizin Berlin, Berlin, GermanyLaboratory of Chronobiology, Charité Universitätsmedizin Berlin, Berlin, GermanyLaboratory of Chronobiology, Charité Universitätsmedizin Berlin, Berlin, Germany; Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, GermanyLaboratory of Chronobiology, Charité Universitätsmedizin Berlin, Berlin, GermanyLaboratory of Chronobiology, Charité Universitätsmedizin Berlin, Berlin, GermanyLocal 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.https://elifesciences.org/articles/62469circadian rhythmsepsismacrophages |
| spellingShingle | Veronika Lang Sebastian Ferencik Bharath Ananthasubramaniam Achim Kramer Bert Maier Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice eLife circadian rhythm sepsis macrophages |
| title | 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_short | Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice |
| title_sort | susceptibility rhythm to bacterial endotoxin in myeloid clock knockout mice |
| topic | circadian rhythm sepsis macrophages |
| url | https://elifesciences.org/articles/62469 |
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