PT  - JOURNAL ARTICLE
AU  - Makeda L. Robinson
AU  - David R. Glass
AU  - Veronica Duran
AU  - Olga Lucia Agudelo Rojas
AU  - Ana Maria Sanz
AU  - Monika Consuegra
AU  - Malaya Kumar Sahoo
AU  - Felix J. Hartmann
AU  - Marc Bosse
AU  - Rosa Margarita Gelvez
AU  - Nathalia Bueno
AU  - Benjamin A. Pinsky
AU  - Jose G. Montoya
AU  - Holden Maecker
AU  - Maria Isabel Estupiñan Cardenas
AU  - Luis Angel Villar Centeno
AU  - Elsa Marina Rojas Garrido
AU  - Fernando Rosso
AU  - Sean C. Bendall
AU  - Shirit Einav
TI  - Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics
AID  - 10.1101/2022.09.21.508901
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.09.21.508901
4099  - http://biorxiv.org/content/early/2022/09/22/2022.09.21.508901.short
4100  - http://biorxiv.org/content/early/2022/09/22/2022.09.21.508901.full
AB  - Approximately five million dengue virus-infected patients, particularly children, progress to a potentially life-threatening severe dengue (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep immune profiling by mass cytometry of PBMCs collected longitudinally from SD progressors (SDp) and uncomplicated dengue (D) patients. While D is characterized by early activation of innate immune responses, in SDp there is rapid expansion and activation of IgG-secreting plasma cells and memory and regulatory T cells. Concurrently, SDp, particularly children, demonstrate increased proinflammatory NK cells, inadequate expansion of CD16+ monocytes, and high expression of the FcγR, CD64 on myeloid cells, yet diminished antigen presentation. Syndrome-specific determinants include suppressed dendritic cell abundance in shock/hemorrhage vs. enriched plasma cell expansion in organ impairment. This study reveals uncoordinated immune responses in SDp and provides insights into SD pathogenesis in humans with potential implications for prediction and treatment.Competing Interest StatementThe authors have declared no competing interest.