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Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics

2023; American Association for the Advancement of Science; Volume: 9; Issue: 12 Linguagem: Inglês

10.1126/sciadv.ade7702

2375-2548

Makeda Robinson, David R. Glass, Verónica Durán, Olga Lucia Agudelo Rojas, Ana María Sanz, Monika Consuegra, Malaya K. Sahoo, Felix J. Hartmann, Marc Bossé, Rosa Margarita Gélvez, Nathalia Bueno, Benjamin A. Pinsky, José G. Montoya, Holden T. Maecker, María Isabel Estupiñán Cárdenas, Luis Villar, Elsa Marina Rojas Garrido, Fernando Rosso, Sean C. Bendall, Shirit Einav,

Viral Infections and Vectors

Approximately 5 million dengue virus-infected patients 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 a signature of diminished antigen presentation. Syndrome-specific determinants include suppressed dendritic cell abundance in shock/hemorrhage versus 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.