Hyperglycemia Inhibits Complement-Mediated Immunological Control ofS. aureusin a Rat Model of Peritonitis

Abstract

Hyperglycemia from diabetes is associated with increased risk of infection fromS. aureusand increased severity of illness. Previous work in our laboratory demonstrated that elevated glucose (>6 mM) dramatically inhibitedS. aureus-initiated complement-mediated immune effectors. Here we reportin vivostudies evaluating the extent to which a hyperglycemic environment alters complement-mediated control ofS. aureusinfection in a rat peritonitis model. Rats were treated with streptozocin to induce diabetes or sham-treated and then inoculated i.p. withS. aureus. Rats were euthanized and had peritoneal lavage at 2 or 24 hours after infection to evaluate early and late complement-mediated effects. Hyperglycemia decreased the influx of IgG and complement components into the peritoneum in response toS. aureusinfection and decreased anaphylatoxin generation. Hyperglycemia decreased C4-fragment and C3-fragment opsonization ofS. aureusrecovered in peritoneal fluids, compared with euglycemic or insulin-rescued rats. Hyperglycemic rats showed decreased phagocytosis efficiency compared with euglycemic rats, which correlated inversely with bacterial survival. These results suggest that hyperglycemia inhibited humoral effector recruitment, anaphylatoxin generation, and complement-mediated opsonization ofS. aureus, suggesting that hyperglycemic inhibition of complement effectors may contribute to the increased risk and severity ofS. aureusinfections in diabetic patients.