Monocyte-associated C1q upregulation and complement activation contribute to vascular endothelial and multi-organ injury in severe dengue
- 1National Center of Technology Innovation for Animal Model, National Human Diseases Animal Model Resource Center, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS & PUMC, Beijing 100021, China
Abstract
Dengue virus (DENV) infection causes a broad spectrum of clinical manifestations, ranging from self-limiting dengue fever (DF) to life-threatening severe dengue (SD). Increased vascular permeability and endothelial dysfunction are hallmarks of SD and contribute to plasma leakage, shock, and multi-organ injury, yet the underlying mechanisms remain incompletely understood. Here, we integrated dynamic bulk and single-cell RNA sequencing data from peripheral blood mononuclear cells (PBMCs) of dengue patients at different disease stages to investigate the mechanisms associated with disease progression. Complement-related signatures were prominently altered in patients with dengue with warning signs (DWS) and SD, with monocytes emerging as a major cellular source of increased C1Q genes (C1QA, C1QB, and C1QC) expression. These findings implicated monocyte-derived C1q and classical complement pathway activation in dengue progression. Using a severe dengue mouse model, we further demonstrated systemic complement activation and deposition of the terminal complement effector membrane attack complex (MAC), which was associated with microvascular endothelial damage and multi-organ injury. Importantly, inhibition of the classical complement pathway with C1INH (C1 esterase inhibitor) significantly alleviated vascular barrier dysfunction and multi-organ injury in severe dengue mice. Collectively, our findings identify monocyte-derived C1q and dysregulated classical complement activation as important contributors to vascular endothelial and multi-organ injury in SD and suggest that targeting the classical complement pathway may represent a potential therapeutic strategy for severe dengue.
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BibTeX
@article{yang2026monocyteassociated,
title = {{Monocyte-associated C1q upregulation and complement activation contribute to vascular endothelial and multi-organ injury in severe dengue}},
author = {Wei Yang and Qian Chen and Nan Yao and Zhe Li and Yi-Teng Zhang and Sheng-Nan Wang and Wei Wang},
journal = {Virologica Sinica},
year = {2026},
month = oct,
doi = {10.1016/j.virs.2026.10.002},
url = {https://doi.org/10.1016/j.virs.2026.10.002},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Monocyte-associated C1q upregulation and complement activation contribute to vascular endothelial and multi-organ injury in severe dengue
AU - Wei Yang
AU - Qian Chen
AU - Nan Yao
AU - Zhe Li
AU - Yi-Teng Zhang
AU - Sheng-Nan Wang
AU - Wei Wang
PY - 2026
DA - 2026/10/07
JO - Virologica Sinica
DO - 10.1016/j.virs.2026.10.002
UR - https://doi.org/10.1016/j.virs.2026.10.002
AB - Dengue virus (DENV) infection causes a broad spectrum of clinical manifestations, ranging from self-limiting dengue fever (DF) to life-threatening severe dengue (SD). Increased vascular permeability and endothelial dysfunction are hallmarks of SD and contribute to plasma leakage, shock, and multi-organ injury, yet the underlying mechanisms remain incompletely understood. Here, we integrated dynamic bulk and single-cell RNA sequencing data from peripheral blood mononuclear cells (PBMCs) of dengue patients at different disease stages to investigate the mechanisms associated with disease progression. Complement-related signatures were prominently altered in patients with dengue with warning signs (DWS) and SD, with monocytes emerging as a major cellular source of increased C1Q genes (C1QA, C1QB, and C1QC) expression. These findings implicated monocyte-derived C1q and classical complement pathway activation in dengue progression. Using a severe dengue mouse model, we further demonstrated systemic complement activation and deposition of the terminal complement effector membrane attack complex (MAC), which was associated with microvascular endothelial damage and multi-organ injury. Importantly, inhibition of the classical complement pathway with C1INH (C1 esterase inhibitor) significantly alleviated vascular barrier dysfunction and multi-organ injury in severe dengue mice. Collectively, our findings identify monocyte-derived C1q and dysregulated classical complement activation as important contributors to vascular endothelial and multi-organ injury in SD and suggest that targeting the classical complement pathway may represent a potential therapeutic strategy for severe dengue.
SN - 1674-0769
SN - 1995-820X
ER -