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Title: Integrated systems immunology approach identifies impaired effector T cell memory responses as a feature of progression to severe dengue fever.
Austin Authors: Ioannidis, Lisa J;Studniberg, Stephanie I;Eriksson, Emily M;Suwarto, Suhendro;Denis, Dionisius;Liao, Yang;Shi, Wei;Garnham, Alexandra L;Sasmono, R Tedjo;Hansen, Diana S
Affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.
Division of Tropical and Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National Hospital (RSCM), Jakarta, Indonesia.
Eijkman Research Center for Molecular Biology, Jakarta, Indonesia.
Olivia Newton-John Cancer Research Institute
Eijkman Research Center for Molecular Biology, Jakarta, Indonesia.
Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.;Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Issue Date: 13-Apr-2023
Date: 2023
Publication information: Journal of Biomedical Science 2023; 30(1)
Abstract: Typical symptoms of uncomplicated dengue fever (DF) include headache, muscle pains, rash, cough, and vomiting. A proportion of cases progress to severe dengue hemorrhagic fever (DHF), associated with increased vascular permeability, thrombocytopenia, and hemorrhages. Progression to severe dengue is difficult to diagnose at the onset of fever, which complicates patient triage, posing a socio-economic burden on health systems. To identify parameters associated with protection and susceptibility to DHF, we pursued a systems immunology approach integrating plasma chemokine profiling, high-dimensional mass cytometry and peripheral blood mononuclear cell (PBMC) transcriptomic analysis at the onset of fever in a prospective study conducted in Indonesia. After a secondary infection, progression to uncomplicated dengue featured transcriptional profiles associated with increased cell proliferation and metabolism, and an expansion of ICOS+CD4+ and CD8+ effector memory T cells. These responses were virtually absent in cases progressing to severe DHF, that instead mounted an innate-like response, characterised by inflammatory transcriptional profiles, high circulating levels of inflammatory chemokines and with high frequencies of CD4low non-classical monocytes predicting increased odds of severe disease. Our results suggests that effector memory T cell activation might play an important role ameliorating severe disease symptoms during a secondary dengue infection, and in the absence of that response, a strong innate inflammatory response is required to control viral replication. Our research also identified discrete cell populations predicting increased odds of severe disease, with potential diagnostic value.
DOI: 10.1186/s12929-023-00916-4
ORCID: 0000-0003-4511-7918
Journal: Journal of Biomedical Science
Start page: 24
PubMed URL: 37055751
ISSN: 1423-0127
Type: Journal Article
Subjects: Dengue fever
Dengue hemorrhagic fever
Effector memory T cells
Non-classical monocytes
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