The evolutionary ecology of circadian rhythms in infection

Abstract

Biological rhythms coordinate organisms' activities with daily rhythms in the environment. For parasites, this includes rhythms in both the external abiotic environment and the within-host biotic environment. Hosts exhibit rhythms in behaviours and physiologies, including immune responses, and parasites exhibit rhythms in traits underpinning virulence and transmission. Yet, the evolutionary and ecological drivers of rhythms in traits underpinning host defence and parasite offence are largely unknown. Here, we explore how hosts use rhythms to defend against infection, why parasites have rhythms, and whether parasites can manipulate host clocks to their own ends. Harnessing host rhythms or disrupting parasite rhythms could be exploited for clinical benefit; we propose an interdisciplinary effort to drive this emerging field forward. Circadian rhythms have long been taken for granted by science. Indeed, the first observation of a clock-controlled behaviour (leaf opening and closing in Mimosa pudica) was not recorded until the 18 th century 1. Following the fundamental observation that organisms can adaptively anticipate daily rhythms in their environment, the field of "chronobiology" took off in the mid-20 th century with a focus on evolutionary and ecological questions. However, the advent of genetic tools a few decades later shifted the remit to determining the molecular and genetic workings of circadian clocks. Yet, despite their assumed major impact on fitness, circadian rhythms remain overlooked in evolutionary ecology 2-4. Here, we propose that the integration of chronobiology and evolutionary ecology return 2 to its roots to tackle a topic of growing and applied interest; the role of rhythms in host-parasite interactions. Note that we use the term "parasite" to collectively refer to all agents of infection (e.g. single-celled and multicellular eukaryotes, bacteria, viruses). One of the most fundamental ecological interactions is that between hosts and parasites. Research from diverse taxa (plants, mammals, and insects) reveals that host clocks drive daily rhythms in immune defences, disease severity and spread 5,6. Parasites display daily rhythms in traits underpinning within-host survival and between-host transmission 7,8. Rhythms in parasite activities and in host responses to infection could provide an advantage to parasites, hosts, both, or neither. To what extent parasites and hosts are in control of their own and/or each other's rhythms is also poorly understood. Understanding the evolution (and possibly, coevolution) of rhythms may enable vaccines and drugs to take advantage of rhythmic vulnerabilities in parasites or harness host rhythms to improve efficacy and reduce drug toxicity. For such interventions to be robust to parasite evolution, understanding how host-parasite interactions shape rhythms in hosts and parasites is necessary 7. Key questions include how rhythms in diverse host traits contribute to defence, how parasites cope with exposure to their host's rhythms, and whether hosts and parasit...

Infection by the castrating parasitic nematode Sphaerularia bombi changes gene expression in Bombus terrestris bumblebee queens

“…Here we identified an enrichment of DEGs associated with circadian rhythm. Within host-parasite interactions, parasites must contend with and can affect host circadian rhythms (Reece et al, 2017;Westwood et al, 2019). This is best documented in parasites of medical importance, where symptoms of infection include irregular circadian rhythms, such as in the case of human infections by parasitic species, such as Plasmodium (Kwiatkowski and Greenwood, 1989) and Trypanosoma species (Rijo-Ferreira et al, 2018).…”

Dawn to Dusk: Diurnal Rhythm of the Immune Response in Rainbow Trout (Oncorhynchus Mykiss)

“…However, on the one hand it is important to consider not only the levels of proinflammatory cytokines, but also the presence of the first-responders in the blood, which can serve as a source of neutrophils and other myeloid cells during the acute phase, prior to the mobilization from their reservoirs in the head kidney. On the other hand, we should keep in perspective that pathogens like bacteria and parasites are also regulated by circadian rhythms [39][40][41], and they eventually manipulate the host rhythmicity for their own benefit [42,43] as viruses do as well [44]. Therefore, "when" a pathogen attacks a host, and how the host defend itself, is a fact regulated by an exquisite balance between the species involved.…”

Host circadian clocks do not set the schedule for the within-host replication of malaria parasites

“…The value of coordinating with daily cycles in, for example, light/dark and temperature in the abiotic environment has long been appreciated, and the importance for parasites of coordinating with rhythms experienced inside hosts and vectors (i.e. the biotic environment), is gaining increasing recognition [1-3]. For example, circadian rhythms in virulence enables the fungal pathogen Botrytis cinerea to cope with rhythmic immune defences in plant hosts [4, 5], circadian control of macrophage migration provides incoming Leishmania major parasites with more host cells to invade at dusk than dawn [6], and host clocks control the ability of herpes and hepatitis viruses to invade cells and to replicate within them [7, 8].…”

“…For example, it has been suggested that the IDC schedule is entirely explained by circadian host immune responses killing certain IDC stages at certain times of day [23] or by only allowing access to a nutrient essential to a particular IDC stage at a certain time-of-day [24]. Alternatively, parasites may be able to, at least in part, schedule their IDC to avoid coinciding a vulnerable IDC stage with a dangerous time-of-day, or to maximally exploit a time-limited resource [3]. A foundation for explaining both why the IDC schedule benefits parasites and how it is controlled, requires discovering which of the myriad of host rhythms associated with the time-of-day of feeding are responsible for the IDC schedule.…”