RESEARCH ARTICLE Cytoplasmic Actin Is an Extracellular Insect Immune Factor which Is Secreted upon Immune Challenge and Mediates Phagocytosis and Direct Killing of Bacteria, and Is a Plasmodium Antagonist

Actin is a highly versatile, abundant, and conserved protein, with functions in a variety of in-tracellular processes. Here, we describe a novel role for insect cytoplasmic actin as an ex-tracellular pathogen recognition factor that mediates antibacterial defense. Insect actins are secreted from cells upon immune challenge through an exosome-independent pathway. Anopheles gambiae actin interacts with the extracellular MD2-like immune factor AgMDL1, and binds to the surfaces of bacteria, mediating their phagocytosis and direct killing. Globu-lar and filamentous actins display distinct functions as extracellular immune factors, and mosquito actin is a Plasmodium infection antagonist. Author Summary Actin is one of the best studied, evolutionary conserved and most abundant intracellular proteins. Actin can exists in globular and filamentous functionally distinct forms, and is involved in a variety of biological processes, such as muscle contraction, cell motility, cell division, vesicle and organelle movement, endocytosis, and cell signaling. Here we show a novel function of insect cytoplasmic actin, as an extracellular immune factor. Actin is ex