Distinct systemic immune responses in asymptomatic and symptomatic dengue virus infection

Sungnak, Waradon; Jiravejchakul, Natnicha; Poonpanichakul, Tiraput; Trakoolsoontorn, Chawinya; Srikor, Sirawit; Opasawatchai, Anunya; Arora, Jantarika; Jevapatarakul, Damita; Thungsatianpun, Narita; Nguantad, Sarintip; Chantaraamporn, Juthamard; Pakchotanon, Pattarakul; Punyadee, Nuntaya; Duangchinda, Thaneeya; Avirutnan, Panisadee; Mongkolsapaya, Juthathip; Meyer, Kerstin B.; Matangkasombut, Oranart; Charoensawan, Varodom; Teichmann, Sarah A.

doi:10.1126/scitranslmed.ads5932

Distinct systemic immune responses in asymptomatic and symptomatic dengue virus infection

Author(s)

Sungnak, Waradon

Jiravejchakul, Natnicha

Poonpanichakul, Tiraput

Trakoolsoontorn, Chawinya

Srikor, Sirawit

Opasawatchai, Anunya

Arora, Jantarika

Jevapatarakul, Damita

Thungsatianpun, Narita

Nguantad, Sarintip

Chantaraamporn, Juthamard

Pakchotanon, Pattarakul

Punyadee, Nuntaya

Duangchinda, Thaneeya

Avirutnan, Panisadee

Mongkolsapaya, Juthathip

Meyer, Kerstin B.

Matangkasombut, Oranart

Charoensawan, Varodom

Teichmann, Sarah A.

Matangkasombut, Ponpan

Sakuntabhai, Anavaj

Singhasivanon, Pratap

Suraamornkul, Swangjit

Yingtaweesak, Tawatchai

Manopwisedjaroen, Khajohnpong

Pitabut, Nada

Thaloengsok, Sasikanya

Date Issued

December 17, 2025

Type

Article

DOI

10.1126/scitranslmed.ads5932

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 IGHA1⁺ 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⁺ 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.

Citation

Science Translational Medicine, 17(829), 2025