Impact of Sleep on Monocytes and Infection

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Dokumentart: Dissertation
Date: 2020-11-20
Language: English
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Biologie
Advisor: Autenrieth, Stella E. (PD Dr.)
Day of Oral Examination: 2020-07-10
DDC Classifikation: 570 - Life sciences; biology
Keywords: Schlaf , Infektion , Immunsystem , Monozyt
License: Publishing license including print on demand
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Sleep has been linked to several vital body functions from memory and metabolism to immunity. The results in this work – showing that sleep in mice has a profound effect on innate immune cells and their ability to fight bacterial infection – support these findings. For the experiments two mice groups were used, sleep mice with 6 h of normal sleep were compared to mice with 6 h of enhanced wakefulness. 6 h of sleep increases the overall cellularity in the blood and spleen of WT mice, in particular the number and frequency of monocytes. This is described in this work as the sleep phenotype, a strong increase in frequency and count of monocytes due to sleep. This phenotype was found for classical monocytes and non-classical monocytes. The increase of monocytes is not due to stress or the progression into macrophages or DCs. Furthermore, no effect of sleep was found on monocytes precursors or their release from the BM. Interestingly, the increase of monocytes in blood and spleen did not lead to a reduction of monocytes in Lymph Nodes, the LP, or the lung. On the contrary, monocyte numbers as well increase in the lung after 6 h of sleep. Furthermore, the sleep phenotype is independent of the ICAM-1-LFA-1 axis and just partially dependent on CCR2. Both are very important factors for the migration of classical monocytes and their contribution to the marginal pool. However, it could be shown that for non-classical monocytes Cx3CR1 is involved in the sleep phenotype. Beyond this, it was demonstrated that the sleep phenotype for classical monocytes is dependent on the Clock gene Arntl, indicating a strong connection between the circadian system and sleep. With regards to immune cell function, sleep increases the ROS production of PMNs and classical monocytes. Consequential this leads to better bacterial clearance and improved survival time upon infection. Taken together sleep is imperative for immune functions and monocyte numbers are highly affected by sleep as well as their ability to fight a bacterial infection. Even though the exact mechanism is not yet fully understood there are strong indications for a connection to the circadian system.

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