Dataset Information

Daily Rhythms of TNF? Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle.

ABSTRACT: The Plasmodium cell cycle, wherein millions of parasites differentiate and proliferate, occurs in synchrony with the vertebrate host's circadian cycle. The underlying mechanisms are unknown. Here we addressed this question in a mouse model of Plasmodium chabaudi infection. Inflammatory gene expression and carbohydrate metabolism are both enhanced in interferon-? (IFN?)-primed leukocytes and liver cells from P. chabaudi-infected mice. Tumor necrosis factor ? (TNF?) expression oscillates across the host circadian cycle, and increased TNF? correlates with hypoglycemia and a higher frequency of non-replicative ring forms of trophozoites. Conversely, parasites proliferate and acquire biomass during food intake by the host. Importantly, cyclic hypoglycemia is attenuated and synchronization of P. chabaudi stages is disrupted in IFN?^-/-, TNF receptor^-/-, or diabetic mice. Hence, the daily rhythm of systemic TNF? production and host food intake set the pace for Plasmodium synchronization with the host's circadian cycle. This mechanism indicates that Plasmodium parasites take advantage of the host's feeding habits.

SUBMITTER: Hirako IC

PROVIDER: S-EPMC6014587 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle.

Hirako Isabella Cristina IC Assis Patrícia Aparecida PA Hojo-Souza Natália Satchiko NS Reed George G Nakaya Helder H Golenbock Douglas Taylor DT Coimbra Roney Santos RS Gazzinelli Ricardo Tostes RT

Cell host & microbe 20180524 6

The Plasmodium cell cycle, wherein millions of parasites differentiate and proliferate, occurs in synchrony with the vertebrate host's circadian cycle. The underlying mechanisms are unknown. Here we addressed this question in a mouse model of Plasmodium chabaudi infection. Inflammatory gene expression and carbohydrate metabolism are both enhanced in interferon-γ (IFNγ)-primed leukocytes and liver cells from P. chabaudi-infected mice. Tumor necrosis factor α (TNFα) expression oscillates across th ...[more]

PMID: 29805094

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Project description:In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus coordinates daily rhythms including sleep-wake, hormone release, and gene expression. The cells of the SCN must synchronize to each other to drive these circadian rhythms in the rest of the body. The ontogeny of circadian cycling and intercellular coupling in the SCN remains poorly understood. Recent in vitro studies have recorded circadian rhythms from the whole embryonic SCN. Here, we tracked the onset and precision of rhythms in PERIOD2 (PER2), a clock protein, within the SCN isolated from embryonic and postnatal mice of undetermined sex. We found that a few SCN cells developed circadian periodicity in PER2 by 14.5 d after mating (E14.5) with no evidence for daily cycling on E13.5. On E15.5, the fraction of competent oscillators increased dramatically corresponding with stabilization of their circadian periods. The cells of the SCN harvested at E15.5 expressed sustained, synchronous daily rhythms. By postnatal day 2 (P2), SCN oscillators displayed the daily, dorsal-ventral phase wave in clock gene expression typical of the adult SCN. Strikingly, vasoactive intestinal polypeptide (VIP), a neuropeptide critical for synchrony in the adult SCN, and its receptor, VPAC2R, reached detectable levels after birth and after the onset of circadian synchrony. Antagonists of GABA or VIP signaling or action potentials did not disrupt circadian synchrony in the E15.5 SCN. We conclude that endogenous daily rhythms in the fetal SCN begin with few noisy oscillators on E14.5, followed by widespread oscillations that rapidly synchronize on E15.5 by an unknown mechanism.SIGNIFICANCE STATEMENT We recorded the onset of PER2 circadian oscillations during embryonic development in the mouse SCN. When isolated at E13.5, the anlagen of the SCN expresses high, arrhythmic PER2. In contrast, a few cells show noisy circadian rhythms in the isolated E14.5 SCN and most show reliable, self-sustained, synchronized rhythms in the E15.5 SCN. Strikingly, this synchrony at E15.5 appears before expression of VIP or its receptor and persists in the presence of blockers of VIP, GABA or neuronal firing. Finally, the dorsal-ventral phase wave of PER2 typical of the adult SCN appears ?P2, indicating that multiple signals may mediate circadian synchrony during the ontogeny of the SCN.

Project description:ObjectiveExercise is a critical component of a healthy lifestyle and a key strategy for the prevention and management of metabolic disease. Identifying molecular mechanisms underlying adaptation in response to chronic physical activity is of critical interest in metabolic physiology. Circadian rhythms broadly modulate metabolism, including muscle substrate utilization and exercise capacity. Here, we define the molecular and physiological changes induced across the daily cycle by voluntary low intensity daily exercise.MethodsWildtype C57BL6/J male and female mice were housed with or without access to a running wheel for six weeks. Maximum running speed was measured at four different zeitgeber times (ZTs, hours after lights on) using either electrical or manual stimulation to motivate continued running on a motorized treadmill. RNA isolated from plantaris muscles at six ZTs was sequenced to establish the impact of daily activity on genome-wide transcription. Patterns of gene expression were analyzed using Gene Set Enrichment Analysis (GSEA) and Detection of Differential Rhythmicity (DODR). Blood glucose, lactate, and ketones, and muscle and liver glycogen were measured before and after exercise.ResultsWe demonstrate that the use of mild electrical shocks to motivate running negatively impacts maximum running speed in mice, and describe a manual method to motivate running in rodent exercise studies. Using this method, we show that time of day influences the increase in exercise capacity afforded by six weeks of voluntary wheel running: when maximum running speed is measured at the beginning of the nighttime active period in mice, there is no measurable benefit from a history of daily voluntary running, while maximum increase in performance occurs at the end of the night. We show that daily voluntary exercise dramatically remodels the murine muscle circadian transcriptome. Finally, we describe daily rhythms in carbohydrate metabolism associated with the time-dependent response to moderate daily exercise in mice.ConclusionsCollectively, these data indicate that chronic nighttime physical activity dramatically remodels daily rhythms of murine muscle gene expression, which in turn support daily fluctuations in exercise performance.

Dataset Information

Daily Rhythms of TNF? Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle.

Publications

Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle.

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