- 作者: Lisa J. Ioannidis, Stephanie I. Studniberg, Emily M. Eriksson, Suhendro Suwarto, Dionisius Denis, Yang Liao, Wei Shi, Alexandra L. Garnham, R. Tedjo Sasmono & Diana S. Hansen
- 作者服務機構: 1.Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia 2.Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia 3.Division of Tropical and Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National Hospital (RSCM), Jakarta, Indonesia 4.Eijkman Research Center for Molecular Biology, Jakarta, Indonesia 5.Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia 6.School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia 7.The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- 中文摘要:
- 英文摘要:
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 CD4low 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. - 中文關鍵字:
- 英文關鍵字: Dengue fever, Dengue hemorrhagic fever, Efector memory T cells, Non-classical monocytes