Anunya Opasawatchai

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.

A comprehensive understanding of dental pulp cellular compositions and their molecular responses to infection are crucial for the advancement of regenerative dentistry. Here, we presented a pilot study of single-cell transcriptomic profiles of 6,810 pulpal cells isolated from a sound human maxillary third molar and three carious teeth with enamel and deep dental caries. We observed altered immune cell compositions of the dental pulp in deep, but not enamel ones. Differential expression analysis revealed up-regulation of several pro-inflammatory, anti-inflammatory, and mineralization-related genes in the immune and stromal cells of the deep dental caries. Making use of an algorithm for predicting cell-to-cell interactions from single-cell transcriptomic profiles, we showed an increase in cell-cell interactions between B cells, plasma cells and macrophages, and other cell types in deep dental caries, including those between TIMP1 (odontoblasts)—CD63 (myeloid cells), and CCL2 (macrophages)—ACKR1 (endothelial cells). Collectively, our work highlighted the single-cell level gene regulations and intercellular interactions in the dental pulps in health and disease.