Distinct systemic immune responses in asymptomatic and symptomatic dengue virus infection

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 <i>IGHA1<sup>+</sup></i> plasmablasts. In contrast, symptomatic dengue cases exhibited indications toward antibody-mediated viral entry, elevated type I interferon responses, and IL-10-associated expansion of <i>IGHG1</i><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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Publication Details

Journal
Science Translational Medicine
Published
2025-12-17
DOI
https://doi.org/10.1126/scitranslmed.ads5932
Citations
1
Primary Topic
Mosquito-borne diseases and control
Type
article
Field-Weighted Citation Impact
1.88
Controls
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article

Distinct systemic immune responses in asymptomatic and symptomatic dengue virus infection

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1 citations
Science Translational Medicine
Mosquito-borne diseases and control
1.88
article

Distinct systemic immune responses in asymptomatic and symptomatic dengue virus infection

Anunya Opasawatchai, Juthamard Chantaraamporn, Tawatchai Yingtaweesak, Anavaj Sakuntabhai, Ponpan Matangkasombut, Thaneeya Duangchinda, Oranart Matangkasombut, Panisadee Avirutnan, Swangjit Suraamornkul, Sarah Amalia Teichmann, Sirawit Srikor, Sasikanya Thaloengsok, Jantarika Kumar Arora, Chawinya Trakoolsoontorn, Nada Pitabut, Juthathip Mongkolsapaya, Pratap Singhasivanon, Sarintip Nguantad, Khajohnpong Manopwisedjaroen, Tiraput Poonpanichakul, Varodom Charoensawan, Nuntaya Punyadee, Pattarakul Pakchotanon, Natnicha Jiravejchakul, Narita Thungsatianpun, Damita Jevapatarakul, Kerstin B. Meyer, Waradon Sungnak
article en
1 citations

Abstract

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 <i>IGHA1<sup>+</sup></i> plasmablasts. In contrast, symptomatic dengue cases exhibited indications toward antibody-mediated viral entry, elevated type I interferon responses, and IL-10-associated expansion of <i>IGHG1</i><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.

Science Translational MedicineVol. 17(829)
Canadian Institute for Advanced Research (CA), National Science and Technology Development Agency (TH), Siriraj Hospital (TH), Centre for Human Genetics (GB), Chulalongkorn University (TH), Wellcome/MRC Cambridge Stem Cell Institute (GB), University of Cambridge (GB), Mahidol University (TH), Wellcome Sanger Institute (GB), Chulabhorn Research Institute (TH), University of Oxford (GB), Mahidol Oxford Tropical Medicine Research Unit (TH), Ramathibodi Hospital (TH), Suranaree University of Technology (TH)
Openalex Percentile: Top 10%
Mosquito-borne diseases and control
1.88
DOISourceOpenAlex
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