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

作者：Hirako Isabella Cristina; Assis Patricia Aparecida; Hojo Souza Natalia Satchiko; Reed George; Nakaya Helder; Golenbock Douglas Taylor; Coimbra Roney Santos; Gazzinelli Ricardo Tostes^*

来源：Cell Host & Microbe, 2018, 23(6): 796-+.

DOI：10.1016/j.chom.2018.04.016

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-gamma (IFN gamma)-primed leukocytes and liver cells from P. chabaudi-infected mice. Tumor necrosis factor alpha (TNF alpha) expression oscillates across the host circadian cycle, and increased TNFa alpha 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 gamma(-/-), TNF receptor(-/-), or diabetic mice. Hence, the daily rhythm of systemic TNF alpha 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

• 出版日期2018-6-13