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.
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Fehervari, Z. Function of the IgM receptor. Nat Immunol 14, 318 (2013). https://doi.org/10.1038/ni.2578
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DOI: https://doi.org/10.1038/ni.2578