Aedes aegypti salivary extracts exert immunomodulatory effects onmacrophages, dendritic cells, and T lymphocytes and increase Zikavirus production in vitro.

Gabriel Hilario, Alison Haubert, Gilson Dorneles, Deise Nascimento Freitas, Onilda Santos Silva, Josiane Somariva Prophiro, Tiago Fazolo, Simone Gonçalves Fonseca, Pedro Roosevelt Torres Romão, Luiz Rodrigues Junior
2024 · doi:10.21203/rs.3.rs-3995109/v1
preprint OA: gold CC-BY-4.0
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Abstract

Abstract Background This study delves into the complex interplay between Aedes aegypti salivary gland extract and immunological cells during Zika virus (ZIKV) infection. Focusing on key immune cells, including macrophages, dendritic cells, and mononuclear cells from human peripheral blood (PBMCs), it aims to unravel the intricate mechanisms through which mosquito saliva possibly modulates the immunological landscape, influencing ZIKV transmission, host susceptibility, and disease progression. The research sheds light on the role of mosquito saliva in enhancing viral replication and impairing cells involved in host defenses, offering new insights into arbovirus pathogenesis and potential intervention strategies. Methods Using the FIOCRUZ-PE243|2015 ZIKV strain, the research evaluates the Aedes aegypt salivary extracts (SGE's) impact on cytokine production in dendritic and macrophage cell lines, as well as its influence on the redox state and cytokine responses in human PBMCs. Flow cytometry assesses immune cell profiling, aiming to understand SGE's role in ZIKV infectivity and immune modulation. Results SGE enhances pro-inflammatory cytokine production in both dendritic cells and macrophages, while also inducing a Th2 cytokine profile, evidenced by decreased IFN-γ and increased IL-4 levels in PBMCs. Furthermore, SGE exposure leads to increased dendritic cell frequencies, altered T lymphocyte dynamics, and elevated oxidative stress markers. Conclusions It highlights how SGE not only facilitates ZIKV infection by modulating cytokine production and oxidative stress but also alters immune cell dynamics.

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License: CC-BY-4.0