Juthamard Chantaraamporn

Mainland Southeast Asia (MSEA) remains under-represented in global immunogenomic references despite its extensive genetic heterogeneity. We present the first single-cell immune atlas of an MSEA population, utilizing Thai individuals from the Asian Immune Diversity Atlas (AIDA) as a representative cohort. We demonstrate that the Thai population is highly genetically diverse, reflecting its history as a geographic nexus for Asian admixture. By integrating single-cell transcriptomics with high-resolution genotyping, we show that genetic ancestry significantly shapes innate immune profiles, specifically CD14⁺ monocytes, highlighting potential evolutionary adaptations to regional pathogens. We identify specific sex-by-ancestry interactions that may drive the baseline activation of pro-inflammatory pathways in females, providing a long-sought cellular rationale for the high prevalence of autoimmune disorders observed in Southeast Asian populations. Ultimately, our study reveals that population-specific genetic architecture dictates immune heterogeneity often missed by self-reported ethnicity or country of origin, providing a critical immunogenomic reference for precision medicine in MSEA regions.

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.