Extracellular matrix protein N-glycosylation mediates immune self-tolerance in <i>Drosophila melanogaster</i>
Nathan T. Mortimer, Mary L. Fischer, Ashley L. Waring, Pooja Kr, Balint Z Kacsoh, Susanna E. Brantley, Erin S. Keebaugh, Joshua Hill, Chris Lark, Julia M. Martin, Pravleen Bains, Jonathan Lee, Alysia D. Vrailas‐Mortimer, Todd A. Schlenke
Abstract
Significance The ability of immune cells to distinguish self tissue from nonself pathogens is a key characteristic of immunity, allowing responses to be targeted against invading pathogens while protecting against self-directed immune damage. The recognition of nonself by innate immune cells has been extensively characterized, but the mechanisms that allow for self recognition and self-tolerance remain largely unexplored. Here, we uncover a self-tolerance system in Drosophila that relies on the N-glycosylation of extracellular matrix proteins: immune activity is restrained by recognition of a self signal and proceeds when encountering self tissues missing the self signal. This allows the host to recognize and protect self tissues, destroy aberrant tissue, and, perhaps, respond to pathogens that evade nonself recognition systems.