The involvement of host circadian clocks in the regulation of the immune response to parasitic infections in mammals

Abstract

Circadian rhythms are recurring variations of physiology with a period of ~24 h, generated by circadian clocks located throughout the body. Studies have shown a circadian regulation of many aspects of immunity. Immune cells have intrinsic clock mechanisms, and innate and adaptive immune responses – such as leukocyte migration, magnitude of inflammation, cytokine production and cell differentiation – are under circadian control. This circadian regulation has consequences for infections including parasitic infections. In the context of Leishmania infection, the circadian clock within host immune cells modulates the magnitude of the infection and the inflammatory response triggered by the parasite. As for malaria, rhythms within the immune system were shown to impact the developmental cycles of Plasmodium parasites within red blood cells. Further, host circadian rhythms impact infections by multicellular parasites; for example, infection with helminth Trichuris muris shows different kinetics of worm expulsion depending on time of day of infection, a variation that depends on the dendritic cell clock. Although the research on the circadian control of immunity in the context of parasitic infections is in its infancy, the research reviewed here suggests a crucial involvement of host circadian rhythms in immunity on the development and progression of parasitic infections.

Diet‐microbiota crosstalk and immunity to helminth infection

“…76 ILC3 deficient in BMAL1, a master regulator of diurnal rhythm, are hyper-active and prone to apoptosis, indicating that sensing of both nutrients and environmental cues calibrate the activity of immune cells (such as ILC3) in the gut. 77 Given that the circadian clock also seems to be tightly associated with immune response to parasites, 78 production of specific gut metabolites in response to food intake or diurnal rhythms may program immune cells to effectively respond to pathogens.…”

Circadian orchestration of host and gut microbiota in infection

“…Responses to fungi and parasites have also been shown to vary depending on time of infection (Carvalho Cabral et al ., 2021; Costantini et al ., 2020). Intravenous infection with Candida albicans in mice at ZT5 shows different symptoms at 6 days p.i.…”

Introduction to biological rhythms: A brief history of chronobiology and its relevance to parasite immunology

“…Parasitic infections often show rhythmic pathology and symptom severity; a result of rhythms in parasitaemia and in host immune responses (reviewed in Refs. [ 90‐92 ]). As discussed above, Plasmodium parasites show periodicity in their replication cycle, leading to rhythms in the resulting inflammatory response and associated fever 82 .…”