A fungal pathogen deploys a small silencing RNA that attenuates mosquito immunity and facilitates infection.

Insecticidal fungi represent a promising alternative to chemical pesticides for disease vector control. Here, we show that the pathogenic fungus Beauveria bassiana exports a microRNA-like RNA (bba-milR1) that hijacks the host RNA-interference machinery in mosquito cells by binding to Argonaute 1 (AGO1). bba-milR1 is highly expressed during fungal penetration of the mosquito integument, and suppresses host immunity by silencing expression of the mosquito Toll receptor ligand Spätzle 4 (Spz4). Later, upon entering the hemocoel, bba-milR1 expression is decreased, which avoids induction of the host proteinase CLIPB9 that activates the melanization response. Thus, our results indicate that the pathogen deploys a cross-kingdom small-RNA effector that attenuates host immunity and facilitates infection.