Now showing 1 - 4 of 4
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    Cytokine and chemokine kinetics in natural human dengue infection as predictors of disease outcome
    (2025-12-01)
    Jiravejchakul, Natnicha
    ;
    Chan-in, Wilawan
    ;
    Thuncharoen, Walairat
    ;
    Pakchotanon, Pattarakul
    ;
    Duangchinda, Thaneeya
    Dengue is an important tropical disease with considerable global impact. Despite this, there remains an urgent need for reliable biomarkers to predict disease severity, as well as effective antiviral drugs and targeted treatments. In this study, we conducted a comprehensive profiling of 41 plasma mediators in patients with asymptomatic dengue (AD) and symptomatic dengue (SD), which includes mild dengue fever (DF) and severe dengue hemorrhagic fever (DHF). Our findings revealed that the levels of nearly all measured mediators were consistently lower in AD compared to SD patients, suggesting a potential protective cytokine response signature. Time-course cytokine analysis in SD shown significantly elevated levels of pro-inflammatory cytokines and chemokines associated with inflammation and viral clearance upon the acute phase, while various growth factors were elevated during the convalescence. Notably, we identified elevated IL-15 levels in DHF patients three days before fever subsidence, highlighting its potential as an early prognostic biomarker for severe disease outcomes. Furthermore, prolonged high levels of IL-8 and IP-10 in DHF during the critical period may contribute to dengue immunopathogenesis. This study advances the understanding of cytokine dynamics in the natural course of human dengue infection, providing valuable insights for the development of targeted treatments and prognostic biomarkers.
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    Item type:Publication,
    Distinct systemic immune responses in asymptomatic and symptomatic dengue virus infection
    (2025-12-17)
    Sungnak, Waradon
    ;
    Jiravejchakul, Natnicha
    ;
    Poonpanichakul, Tiraput
    ;
    Trakoolsoontorn, Chawinya
    ;
    Srikor, Sirawit
    A comprehensive understanding of human systemic immune responses to mosquito-borne dengue virus (DENV) infection is vital for addressing challenges posed by viral heterologous serotypes and potential adverse memory immune responses. Asymptomatic DENV infection offers an opportunity to explore protective immunity because infected individuals effectively clear the virus without symptomatic manifestations. However, data on asymptomatic dengue are scarce because of limited sample availability during silent viremia. Here, we conducted single-cell RNA and immune receptor sequencing of peripheral blood mononuclear cells (PBMCs) from donors with varying disease severities including asymptomatic dengue and performed longitudinal analysis in a symptomatic dengue cohort, enabling identification of distinct immune responses. In asymptomatic dengue, we observed potential indications of enhanced viral antigen processing via MHC-I, correlating with increased CD8 effector T cell activities, distinct NK cell profiles, and enriched IGHA1<sup>+</sup> plasmablasts. In contrast, symptomatic dengue cases exhibited indications toward antibody-mediated viral entry, elevated type I interferon responses, and IL-10–associated expansion of IGHG1<sup>+</sup> plasmablasts with biased V(D)J gene usage and a shared B cell receptor clonotype network. Our study reports a gene expression and immune receptor repertoire resource for systemic immune responses to DENV infection and suggests distinct mechanisms for potential protection and pathogenicity in individuals with asymptomatic compared with symptomatic dengue.
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    Item type:Publication,
    Anti-DENV IgE correlates with dengue severity and triggers FcεRI-dependent basophil activation inhibited by Omalizumab
    (2026-12-01)
    Chan-in, Wilawan
    ;
    Vacharathit, Vimvara
    ;
    Tancharoen, Walairat
    ;
    Duangchinda, Thaneeya
    ;
    Mongkolsapaya, Juthathip
    Severe dengue, marked by plasma leakage, is often linked to secondary heterotypic dengue virus (DENV) infection. While mast cells and basophils contribute to dengue pathogenesis, the role of anti-DENV IgE remains unclear. Here, we investigated whether anti-DENV IgE promotes FcεRI-dependent basophil activation, potentially contributing to disease severity. Plasma from dengue fever (DF, n = 42) and dengue hemorrhagic fever (DHF, n = 56) patients, collected at febrile, defervescence, and convalescent phases, were analyzed using an in-house IgE-capture ELISA developed to detect antibodies against all four DENV serotypes. Functional assays employed RS-ATL8, a human FcεRI-expressing basophil reporter cell line, to assess IgE-mediated activation following DENV antigen cross-linking. The anti-IgE monoclonal antibody Omalizumab was used to evaluate FcεRI dependence. Anti-DENV IgE was detected in both DF and DHF, peaking at defervescence and significantly higher in DHF. Total IgE was elevated but did not differ between groups. About one-third of anti-DENV-IgE-positive plasma samples induced RS-ATL8 activation upon DENV challenge, an effect abolished by omalizumab. These findings indicate a potential pathogenic role of anti-DENV IgE and provide a rationale for further investigation of IgE-targeted interventions.
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    Item type:Publication,
    Heterogeneity and dynamics of DENV-specific CD8 + T cells in dengue infection
    (2026-12-01)
    Srikor, Sirawit
    ;
    Sungnak, Waradon
    ;
    Trakoolsoontorn, Chawinya
    ;
    Poonpanichakul, Tiraput
    ;
    Jiravejchakul, Natnicha
    Dengue virus (DENV) is a major global health threat, with secondary heterotypic infections potentially inducing detrimental memory immune responses. Antigen-specific CD8 + T cells contribute to both protection and pathogenicity, yet how their phenotypic heterogeneity relates to disease severity remains unclear. Here, we performed plate-based single-cell RNA sequencing of circulating DENV-specific CD8 + T cells identified by HLA tetramers loaded with DENV NS3-derived epitopes. Using tetramer binding to peptides corresponding to the currently and serologically inferred dominant previously infecting serotypes, we identify distinct CD8 + T cell subsets associated with disease severity. Asymptomatic dengue is enriched for lower tetramer binding cells with moderate cytotoxic programs, whereas dengue hemorrhagic fever is associated with high tetramer binding CX3CR1 + CD8 + T cells exhibiting enhanced expression of genes related to T cell receptor signaling and cytotoxicity. T cell receptor repertoires are similar among symptomatic cases but displayed temporal dynamics. Overall, DENV NS3-specific CD8 + T cells across disease severity and time are associated with distinct transcriptomic states and T cell receptor features.