Abstract
The daily periodicity of the Earth’s rotation around the Sun, referred to as circadian (Latin “circa” = about, and “diem” = day), is also mirrored in the behavior and metabolism of living beings. The discovery that dedicated cellular genes control various aspects of this periodicity has led to studies of the molecular mechanism of the circadian response at the cellular level. It is now established that the circadian genes impact on a large network of hormonal, metabolic, and immunological pathways, affecting multiple aspects of biology. Recent studies have extended the role of the circadian system to the regulation of infection, host–pathogen interaction, and the resultant disease outcome. This critical review summarizes our current knowledge of circadian-pathogen interaction at both systemic and cellular levels, but with emphasis on the molecular aspects of the regulation. Wherever applicable, the potential of a direct interaction between circadian factors and pathogenic macromolecules is also explored. Finally, this review offers new directions and guidelines for future research in this area, which should facilitate progress.
Highlights
Sunrise and sunset bring us day and night in a 24-h cycle due to the rotation of the Earth around its own axis
Phenotypic studies of clock mutations have traditionally focused on general biology and physiology, and found a plethora of abnormalities that appear to belong to three main categories: Metabolic syndrome [45], aging, and immune dysregulation (Table 2 in reference [46])
The ability of E. coli and Klebsiella pneumonia to escape the gut microbiome should be affected by alteration of innate immunity during the day and night cycle, and by sleep disturbances that are common in the elderly, the sick, and the caregivers working in night shifts, who are exposed to nosocomial infections
Summary
Sunrise and sunset bring us day and night in a 24-h cycle due to the rotation of the Earth around its own axis. Visible light is detected by retinal photoreceptors, and the signal is transduced to the so-called “master clock” in the suprachiasmatic nucleus (SCN) in the hypothalamus [1]. The existence of an “endogenous” timekeeper that operates autonomously without any direct light signal was recognized early on and termed the “circadian clock”(CC). While it was always obvious to the most casual observer that all animals follow the day and night cycle in their daily behavior—and the phototropism of plants was extensively studied—the molecular underpinning of the CC began with the revelation that it is entrained in virtually every tissue of the body as well as in single cells. I apologize to the many scientists whose original early research papers were not directly referenced
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