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
Affiliations
Edgar Ruz Fernandes
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil
Marcela Luize Barbosa
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil
Marcelo Pires Amaral
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil
Juliana de Souza Apostolico
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil; Institute for Investigation in Immunology (iii)-INCT, São Paulo, Brazil
Fernando Bandeira Sulczewski
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
Sergio Tufik
Department of Psychobiology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil
Monica Levy Andersen
Department of Psychobiology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil
Silvia Beatriz Boscardin
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii)-INCT, São Paulo, Brazil
Alexandre Castro Keller
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil; Corresponding author
Daniela Santoro Rosa
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil; Institute for Investigation in Immunology (iii)-INCT, São Paulo, Brazil; Corresponding author
Summary: 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.
