Sleep Disturbance during Infection Compromises Tfh Differentiation and Impacts Host Immunity

Edgar Ruz Fernandes; Marcela Luize Barbosa; Marcelo Pires Amaral; Juliana de Souza Apostolico; Fernando Bandeira Sulczewski; Sergio Tufik; Monica Levy Andersen; Silvia Beatriz Boscardin; Alexandre Castro Keller; Daniela Santoro Rosa

doi:10.1016/j.isci.2020.101599

Sleep Disturbance during Infection Compromises Tfh Differentiation and Impacts Host Immunity

iScience. 2020 Sep 23;23(10):101599. doi: 10.1016/j.isci.2020.101599. eCollection 2020 Oct 23.

Affiliations

¹ Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil.
² Institute for Investigation in Immunology (iii)-INCT, São Paulo, Brazil.
³ Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
⁴ Department of Psychobiology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil.

Abstract

Although the influence of sleep quality on the immune system is well documented, the mechanisms behind its impact on natural host immunity remain unclear. Meanwhile, it has been suggested that neuroimmune interactions play an important role in this phenomenon. To evaluate the impact of stress-induced sleep disturbance on host immunity, we used a murine model of rapid eye movement sleep deprivation (RSD) integrated with a model of malaria blood-stage infection. We demonstrate that sleep disturbance compromises the differentiation of T follicular helper cells, increasing host susceptibility to the parasite. Chemical inhibition of glucocorticoid (Glcs) synthesis showed that abnormal Glcs production compromised the transcription of Tfh-associated genes resulting in impaired germinal center formation and humoral immune response. Our data demonstrate that RSD-induced abnormal activation of the hypothalamic-pituitary-adrenal axis drives host susceptibility to infection. Understanding the impact of sleep quality in natural resistance to infection may provide insights for disease management.

Keywords: Behavioral Neuroscience; Immunology.