Tick saliva reprograms macrophages into immunosuppressive hubs that regulate T-cell immunity in Rhipicephalus microplus infestation

Abstract Ticks transmit diverse pathogens and secrete saliva with immunomodulatory properties that facilitates blood feeding. However, the cellular mechanisms underlying saliva-mediated immune suppression remain poorly defined. Here, we identify macrophages as the central hub through which saliva from the cattle tick Rhipicephalus microplus suppresses T-cell mediated immunity. Tick saliva inhibited IFN-γ and TNF production by CD4⁺ and CD8⁺ T cells while enhancing IL-10 and TGF-β expression, particularly in regulatory T cells. These effects were lost upon removal of CD14⁺ cells, underscoring the importance of macrophage-lineage cells in saliva-induced immunosuppression. Transcriptomic and functional analyses showed that tick saliva reprograms macrophages into an immunosuppressive state with reduced MHC class II, attenuated proinflammatory signaling, and suppressed chemokine production. Consistent with these findings, immunofluorescence analysis of tick-feeding sites showed an increased presence of IL-10–expressing macrophages and T cells. Our findings highlight a strategy by which arthropod saliva suppresses host immunity to facilitate pathogen transmission.