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Physiological trade-offs between mosquito immune response and reproductive capability can arise due to insufficient resource availability. C-type lectin family members may be involved in these processes. We established a GCTL-3-/- mutant Aedes aegypti using CRISPR/Cas9 to investigate the role of GCTL-3 in balancing the costs associated with immune responses to arboviral infection and reproduction. GCTL-3-/- mutants showed significantly reduced DENV-2 infection rate and gut commensal microbiota populations, as well as upregulated JAK/ST