| Title: |
Immune profiling in subclinical secondary dengue-infected cases reveals adaptive immune signatures correlated to protection from severe dengue |
| Authors: |
Gonnella, Giorgio; Libri, Valentina; Gioacchino, Emanuele; Mella, Sébastien; Sann, Sotheary; Sorn, Sopheak; Ken, Sreymom; Seffer, Valerie; Ya, Nisa; Heng, Leangyi; Yay, Chantana; Sakuntabhai, Anavaj; Ly, Sowath; Dussart, Philippe; Duong, Veasna; Hasan, Milena; Cantaert, Tineke |
| Contributors: |
Institut Pasteur du Cambodge; Pasteur Network (Réseau International des Instituts Pasteur); UTechS Single Cell Biomarkers (CB UTechS); Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Istituto Superiore di Sanità = Italian National Institute of Health Roma, Italia (ISS); Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB; Jayavarman VII Hospital Siem Reap, Cambodia; Écologie et Émergence des Pathogènes Transmis par les Arthropodes / Ecology and Emergence of Arthropod-borne Pathogens; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Unité de Virologie / Virology Unit Phnom Penh; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur); Institut Pasteur de Madagascar; This work was funded by NIH (PICREID,1U01AI151758), Janssen Horizon, and the Institut Pasteur PTR Program (#2019-212). The laboratory of T.C. is funded by NIH (PICREID-U01 AI151758, R01 AI175134, and R01 AI137276), Horizon Europe (grant no. 101137033), ANR (grant no. AAPG2023), and Wellcome Trust (grant no. 311543/Z/24/Z).; We would like to thank all participating clinicians from the Kampong Cham and Kampong Thom provincial hospitals, Baray and Steung district hospitals, and Jayavaraman VII hospital in Siem Reap for their help in patient recruitment. We would like to thank Estelle Mottez from the Institut Pasteur Paris Coordination Pole for Clinical Research for support in ethical procedures. We would like to thank Huy Rekol and Rithea Leang from the National Dengue Control Program for their support. We would like to thank Ratana Meng, Nisa Ya, Sokchea Lay, and Borita Heng for their help in sample processing. We would like to thank Sopheap Oeng for help in testing the computational pipeline and cleaning up its source code.; European Project: 101137033,HORIZON-HLTH-2023-DISEASE-03,HORIZON-HLTH-2023-DISEASE-03,CCHFVACIM(2024) |
| Source: |
ISSN: 1931-3128 ; Cell Host & Microbe ; https://riip.hal.science/pasteur-05315617 ; Cell Host & Microbe, 2025, 33 (7), pp.1191-1207.e4. ⟨10.1016/j.chom.2025.06.006⟩. |
| Publisher Information: |
CCSD |
| Publication Year: |
2025 |
| Subject Terms: |
antibody-dependent enhancement; type I IFN; DENV-specific T cells; correlates of protection; subclinical dengue; [SDV]Life Sciences [q-bio]; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.5281/zenodo.15542908; info:eu-repo/semantics/altIdentifier/pmid/40580952; info:eu-repo/grantAgreement//101137033/EU/Crimean-Congo Haemorrhagic Fever Vaccine and Immunotherapy/CCHFVACIM; PUBMED: 40580952 |
| DOI: |
10.1016/j.chom.2025.06.006 |
| Availability: |
https://riip.hal.science/pasteur-05315617; https://riip.hal.science/pasteur-05315617v1/document; https://riip.hal.science/pasteur-05315617v1/file/PIIS1931312825002355.pdf; https://doi.org/10.1016/j.chom.2025.06.006 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.CB9C8A50 |
| Database: |
BASE |