Toso is a plasma membrane protein expressed by many cell types of the immune system and acts as an Fc receptor for immunoglobulin M but can also inhibit proapoptotic signals. In the Proceedings of the National Academy of Sciences, Mak and colleagues demonstrate a further important function for this molecule in modulating phagocyte activation. The authors generate Toso-deficient mice and find no obvious defects in the development of their phagocytes; however, in response to various activators, Toso-deficient granulocytes produce a greater abundance of reactive oxygen species (ROS). Conversely, signaling via Toll-like receptors, production of inflammatory cytokines, phagocytosis of Listeria and sepsis induction are all diminished in Toso-deficient phagocytes. Finally, the authors find that the Toso-deficient mice have impaired resistance in a Listeria infection model. Toso therefore seems to exert dual functions in phagocytes by inhibiting programmed cell death but also diminishing their activation threshold to a variety of triggers, most probably in an immunoglobulin M–dependent manner.

Proc. Natl. Acad. Sci. USA 110, 2593–2598 (2013)