Dengue Virus Serotype 2 Infection Transcriptionally Reprograms Host Neutrophils to Establish an Immunosuppressive Microenvironment in Mice
- 1Laboratory of Virology, Regional Centre for Biotechnology, Faridabad, India
Abstract
Dengue virus (DV) infection triggers profound alterations in host immune responses, yet the transcriptomic reprogramming of innate immune cells during disease progression remains incompletely understood. Here, we demonstrated that Dengue virus serotype 2 (DV-2) infection transcriptionally reprograms host neutrophils, establishing an immunosuppressive microenvironment that facilitates pathogenesis. Through scRNA transcriptomic profiling of bone marrow and spleen cells from the DV-2-infected AG129 mouse model, we delineated a distinct neutrophil signature that shows dynamic shifts in immature and activated populations over the course of dengue infection. We also characterized a specific Ly6Glow subpopulation, notably Fibrinogen-like protein 2 (FGL2)-expressing subsets, that appeared with disease progression. Serum FGL2 levels were significantly elevated in both DV-2-infected mice and human dengue-positive patients. Furthermore, treatment of splenocytes with FGL2 or FGL2-enriched neutrophil secretomes suppressed T cell functional activity and promoted an immunosuppressive phenotype. Together, these findings reveal how DV-2-driven neutrophil reprogramming shapes an immunosuppressive network, highlighting the importance of studying FGL2-expressing neutrophil subsets to understand dengue immunopathogenesis.
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BibTeX
@misc{rawat2026dengue,
title = {{Dengue Virus Serotype 2 Infection Transcriptionally Reprograms Host Neutrophils to Establish an Immunosuppressive Microenvironment in Mice}},
author = {S. Rawat and A. Chhetri and S. Nimesh and A. D. Pandey and S. Sadhu and G. Siddqui and S. Samal and A. Awasthi and A. Banerjee},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762704},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762704v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Dengue Virus Serotype 2 Infection Transcriptionally Reprograms Host Neutrophils to Establish an Immunosuppressive Microenvironment in Mice
AU - S. Rawat
AU - A. Chhetri
AU - S. Nimesh
AU - A. D. Pandey
AU - S. Sadhu
AU - G. Siddqui
AU - S. Samal
AU - A. Awasthi
AU - A. Banerjee
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762704
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762704v1
AB - Dengue virus (DV) infection triggers profound alterations in host immune responses, yet the transcriptomic reprogramming of innate immune cells during disease progression remains incompletely understood. Here, we demonstrated that Dengue virus serotype 2 (DV-2) infection transcriptionally reprograms host neutrophils, establishing an immunosuppressive microenvironment that facilitates pathogenesis. Through scRNA transcriptomic profiling of bone marrow and spleen cells from the DV-2-infected AG129 mouse model, we delineated a distinct neutrophil signature that shows dynamic shifts in immature and activated populations over the course of dengue infection. We also characterized a specific Ly6Glow subpopulation, notably Fibrinogen-like protein 2 (FGL2)-expressing subsets, that appeared with disease progression. Serum FGL2 levels were significantly elevated in both DV-2-infected mice and human dengue-positive patients. Furthermore, treatment of splenocytes with FGL2 or FGL2-enriched neutrophil secretomes suppressed T cell functional activity and promoted an immunosuppressive phenotype. Together, these findings reveal how DV-2-driven neutrophil reprogramming shapes an immunosuppressive network, highlighting the importance of studying FGL2-expressing neutrophil subsets to understand dengue immunopathogenesis.
ER -