Integrated systems immunology approach identifies impaired effector T cell memory responses as a feature of progression to severe dengue fever

Ioannidis, LJ; Studniberg, SI; Eriksson, EM; Suwarto, S; Denis, D; Liao, Y; Shi, W; Garnham, AL; Sasmono, RT; Hansen, DS

Author(s): Ioannidis, LJ; Studniberg, SI; Eriksson, EM; Suwarto, S; Denis, D; Liao, Y; Shi, W; Garnham, AL; Sasmono, RT; Hansen, DS;
Details: Publication Year 2023-04-13,Volume 30,Issue #1,Page 24
Journal Title: Journal of Biomedical Science
Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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 CD4(low) non-classical monocytes predicting increased odds of severe disease. CONCLUSIONS: 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.
Publisher: BMC
Keywords: Dengue fever; Dengue hemorrhagic fever; Effector memory T cells; Non-classical monocytes
Research Division(s): Bioinformatics; Population Health And Immunity; Infectious Diseases And Immune Defence
PubMed ID: 37055751
Publisher's Version: https://doi.org/10.1186/s12929-023-00916-4
Open Access at Publisher's Site: https://doi.org/10.1186/s12929-023-00916-4
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: s12929-023-00916-4.pdf - (9.77MB, application/pdf)

Creation Date: 2023-04-18 01:58:46

Last Modified: 2023-04-18 02:52:14