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