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      A Tangled Threesome: Circadian Rhythm, Body Temperature Variations, and the Immune System

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          Abstract

          Simple Summary

          In mammals, including humans, the body temperature displays a circadian rhythm and is maintained within a narrow range to facilitate the optimal functioning of physiological processes. Body temperature increases during the daytime and decreases during the nighttime thus influencing the expression of the molecular clock and the clock-control genes such as immune genes. An increase in body temperature (daytime, or fever) also prepares the organism to fight aggression by promoting the activation, function, and delivery of immune cells. Many factors may affect body temperature level and rhythm, including environment, age, hormones, or treatment. The disruption of the body temperature is associated with many kinds of diseases and their severity, thus supporting the assumed association between body temperature rhythm and immune functions. Recent studies using complex analysis suggest that circadian rhythm may change in all aspects (level, period, amplitude) and may be predictive of good or poor outcomes. The monitoring of body temperature is an easy tool to predict outcomes and maybe guide future studies in chronotherapy.

          Abstract

          The circadian rhythm of the body temperature (CRBT) is a marker of the central biological clock that results from multiple complex biological processes. In mammals, including humans, the body temperature displays a strict circadian rhythm and has to be maintained within a narrow range to allow optimal physiological functions. There is nowadays growing evidence on the role of the temperature circadian rhythm on the expression of the molecular clock. The CRBT likely participates in the phase coordination of circadian timekeepers in peripheral tissues, thus guaranteeing the proper functioning of the immune system. The disruption of the CRBT, such as fever, has been repeatedly described in diseases and likely reflects a physiological process to activate the molecular clock and trigger the immune response. On the other hand, temperature circadian disruption has also been described as associated with disease severity and thus may mirror or contribute to immune dysfunction. The present review aims to characterize the potential implication of the temperature circadian rhythm on the immune response, from molecular pathways to diseases. The origin of CRBT and physiological changes in body temperature will be mentioned. We further review the immune biological effects of temperature rhythmicity in hosts, vectors, and pathogens. Finally, we discuss the relationship between circadian disruption of the body temperature and diseases and highlight the emerging evidence that CRBT monitoring would be an easy tool to predict outcomes and guide future studies in chronotherapy.

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          Most cited references122

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          Generation of circadian rhythms in the suprachiasmatic nucleus

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            Fever and the thermal regulation of immunity: the immune system feels the heat.

            Fever is a cardinal response to infection that has been conserved in warm-blooded and cold-blooded vertebrates for more than 600 million years of evolution. The fever response is executed by integrated physiological and neuronal circuitry and confers a survival benefit during infection. In this Review, we discuss our current understanding of how the inflammatory cues delivered by the thermal element of fever stimulate innate and adaptive immune responses. We further highlight the unexpected multiplicity of roles of the pyrogenic cytokine interleukin-6 (IL-6), both during fever induction and during the mobilization of lymphocytes to the lymphoid organs that are the staging ground for immune defence. We also discuss the emerging evidence suggesting that the adrenergic signalling pathways associated with thermogenesis shape immune cell function.
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              Diet and feeding pattern affect the diurnal dynamics of the gut microbiome.

              The gut microbiome and daily feeding/fasting cycle influence host metabolism and contribute to obesity and metabolic diseases. However, fundamental characteristics of this relationship between the feeding/fasting cycle and the gut microbiome are unknown. Our studies show that the gut microbiome is highly dynamic, exhibiting daily cyclical fluctuations in composition. Diet-induced obesity dampens the daily feeding/fasting rhythm and diminishes many of these cyclical fluctuations. Time-restricted feeding (TRF), in which feeding is consolidated to the nocturnal phase, partially restores these cyclical fluctuations. Furthermore, TRF, which protects against obesity and metabolic diseases, affects bacteria shown to influence host metabolism. Cyclical changes in the gut microbiome from feeding/fasting rhythms contribute to the diversity of gut microflora and likely represent a mechanism by which the gut microbiome affects host metabolism. Thus, feeding pattern and time of harvest, in addition to diet, are important parameters when assessing the microbiome's contribution to host metabolism.
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                Author and article information

                Journal
                Biology (Basel)
                Biology (Basel)
                biology
                Biology
                MDPI
                2079-7737
                18 January 2021
                January 2021
                : 10
                : 1
                : 65
                Affiliations
                [1 ]Microbes Evolution Phylogénie et Infection, Institut Recherche et Développement, Aix-Marseille University, 13005 Marseille, France; ayebailo66@ 123456gmail.com (A.B.D.); soraya.mezouar@ 123456univ-amu.fr (S.M.); marc.leone@ 123456ap-hm.fr (M.L.)
                [2 ]Institut Hospitalo-Universitaire-Méditerranée Infection, Assistance Publique-Hôpitaux de Marseille, 13005 Marseille, France
                [3 ]Médecine Intensive-Réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, 13915 Marseille, France
                [4 ]Service d’Anesthésie et de Réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, 13915 Marseille, France
                Author notes
                [* ]Correspondence: bcoiffard.aphm@ 123456gmail.com (B.C.); jean-louis.mege@ 123456univ-amu.fr (J.-L.M.); Tel.: +33-4-91-96-61-33 (B.C.); +33-4-13-73-20-51 (J.-L.M.); Fax: +33-4-13-73-20-52 (J.-L.M.)
                Author information
                https://orcid.org/0000-0002-8896-5346
                https://orcid.org/0000-0002-2285-7051
                Article
                biology-10-00065
                10.3390/biology10010065
                7829919
                33477463
                5bbbe3ea-73f7-4924-9f15-5ed6c306b2a7
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 December 2020
                : 10 January 2021
                Categories
                Review

                body temperature,circadian rhythm,chronobiology disorders,immunity,disease

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