» Articles » PMID: 36595532

Longitudinal Proteomic Profiling of the Inflammatory Response in Dengue Patients

Abstract

Background: The immunopathogenesis of dengue virus (DENV) infection remains incompletely understood. To increase our understanding of inflammatory response in non-severe dengue, we assessed longitudinal changes in the inflammatory proteome in patients with an acute DENV infection.

Methods: Using a multiplex proximity extension assay (PEA), we measured relative levels of 368 inflammatory markers in plasma samples from hospitalized patients with non-severe DENV infection in the acute (n = 43) and convalescence (n = 35) phase of the infection and samples of healthy controls (n = 10).

Results: We identified 203 upregulated and 39 downregulated proteins in acute versus convalescent plasma samples. The upregulated proteins had a strong representation of interferon (IFN) and IFN-inducible effector proteins, cytokines (e.g. IL-10, IL-33) and cytokine receptors, chemokines, pro-apoptotic proteins (e.g. granzymes) and endothelial markers. A number of differentially expressed proteins (DEPs) have not been reported in previous studies. Functional network analysis highlighted a central role for IFNγ, IL-10, IL-33 and chemokines. We identified different novel associations between inflammatory proteins and circulating concentrations of the endothelial glycocalyx disruption surrogate marker syndecan-1. Conclusion: This unbiased proteome analysis provides a comprehensive insight in the inflammatory response in DENV infection and its association with glycocalyx disruption.

References
1.
Devignot S, Sapet C, Duong V, Bergon A, Rihet P, Ong S . Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue. PLoS One. 2010; 5(7):e11671. PMC: 2907396. DOI: 10.1371/journal.pone.0011671. View

2.
Wilkinson L, Gilbert T, Kinna G, Ruta L, Pennisi D, Kett M . Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development. J Am Soc Nephrol. 2007; 18(6):1697-708. DOI: 10.1681/ASN.2006091012. View

3.
Jadhav M, Nayak M, Kumar S, Venkatesh A, Patel S, Kumar V . Clinical Proteomics and Cytokine Profiling for Dengue Fever Disease Severity Biomarkers. OMICS. 2017; 21(11):665-677. DOI: 10.1089/omi.2017.0135. View

4.
Chapouly C, Hollier P, Guimbal S, Cornuault L, Gadeau A, Renault M . Desert Hedgehog-Driven Endothelium Integrity Is Enhanced by Gas1 (Growth Arrest-Specific 1) but Negatively Regulated by Cdon (Cell Adhesion Molecule-Related/Downregulated by Oncogenes). Arterioscler Thromb Vasc Biol. 2020; 40(12):e336-e349. DOI: 10.1161/ATVBAHA.120.314441. View

5.
Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View