Impaired mTOR Signaling Causes Immune Suppression in Diabetes

Abstract It is estimated that over 11% of the U.S. population has diabetes and 38% adult pre-diabetic. Diabetes carries increased risk severity many infections, which been attributed to defects in innate immune system. Despite high impact on infection, underlying mechanisms dysfunction diabetic host have yet be fully elucidated. We recently shown cells a environment cannot undergo respiratory burst reactive oxygen species nitric oxide response infection with Staphylococcus aureus, most common pathogen associated frequently severe invasive skin soft tissue (SSTI) patients diabetes. The inhibition was due activation-dependent expression glucose transporter GLUT1, required for neutrophils macrophages. therefore sought further elucidate specific by phagocytes are impaired their ability control S. aureusSSTI. observed mTOR signaling mouse model aureusSSTI, upstream both GLUT-1 expression. Inhibition rapamycin phenocopies higher bacterial burden during as well activity upon macrophage activation absence insulin growth factor signaling. These findings begin role mechanism suppression caused