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

Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil / Division of Infectious Diseases and Immunology. University of Massachusetts Medical School. Worcester, MA, USA.
Division of Infectious Diseases and Immunology. University of Massachusetts Medical School. Worcester, MA, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Division of Preventive and Behavioral Medicine. University of Massachusetts Medical School. Worcester, MA, USA.
Universidade de São Paulo. Escola de Ciências Farmacêuticas. São Paulo, SP, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil / Division of Infectious Diseases and Immunology. University of Massachusetts Medical School. Worcester, MA, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil / Division of Infectious Diseases and Immunology. University of Massachusetts Medical School. Worcester, MA, USA / Fundação Oswaldo Cruz. Plataforma de Medicina Translacional. Ribeirão Preto, SP, Brasil / Faculdade de Medicina de Ribeirão Preto. Ribeirão Preto, SP, Brasil.

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

Keywords in Portuguese

IFNγ
Plasmodium
TNFα

Keywords

IFNγ
Plasmodium
TNFα
Energy metabolism
Food intake
Glucose
Insulin
Malaria and circadian cycle

Publisher

Elsevier

Citation

HIRAKO, Isabella Cristina et al. Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle. Cell Host and Microbe, v. 23, n. 6, p. 796-808, 2018.

DOI

10.1016/j.chom.2018.04.016

ISSN

1931-3128

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/33685

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Copyright

Restricted access

Embargo date

2080-01-01

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