Immune profiling in subclinical secondary dengue-infected cases reveals adaptive immune signatures correlated to protection from severe dengue
Giorgio Gonnella, Valentina Libri, Emanuele Gioacchino, Sébastien Mella, Sotheary Sann, Sopheak Sorn, Sreymom Ken, Valérie Seffer, Nisa Ya, Leangyi Heng, Chantana Yay, Anavaj Sakuntabhai, Sowath Ly, Philippe Dussart, Veasna Duong, Milena Hasan, Tineke Cantaert
Abstract
Development of strategies to prevent severe dengue has been challenging, partly by our incomplete understanding of a protective immune response after dengue virus (DENV) infection. To define adaptive immune signatures associated with protection from hospitalized dengue, we performed in-depth single-cell immunoprofiling and quantified DENV-specific T cells in subclinical or hospitalized dengue-infected children. Individuals with subclinical infection exhibit clonally expanded CD4 + TEMRA cells, increased frequency of DENV-specific CD4 + T cells, and demonstrate a gene expression signature of increased Treg functionality. Across all T cell subsets, subclinical cases upregulated a type I IFN response gene signature. In contrast, expanding CD8 + EM cells from hospitalized patients express more inhibitory markers and fewer cytotoxic proteins. In addition, hospitalized dengue is characterized by high frequencies and clonally expanded immunoglobulin G (Ig)G1-expressing plasmablasts. These findings identify candidate correlates of protection and support a rationale for T cell-directed interventions for dengue disease.