Enhanced susceptibility of mice with streptozotocin-induced diabetes to type II group B streptococcal infection

Abstract

Since diabetes mellitus predisposes adults to group B streptococcal (GBS) bacteremia, a murine model of streptozotocin-induced diabetes and type II GBS bacteremia was developed to assess certain immune factors which might influence susceptibility to infection. In diabetic mice, the 50% lethal dose for two strains of type II GBS was significantly lower (greater than 1 log10 decrease in CFU per milliliter) than in control animals. This enhanced virulence of GBS for diabetic animals was associated with prolonged bacteremia, persistent sequestration of organisms in the splanchnic reticuloendothelial system, and a shift from splenic to hepatic clearance. Although immunization of control and diabetic animals resulted in high concentrations of type-specific serum antibody, it had no effect on late reticuloendothelial system sequestration in diabetics. In contrast, depletion of complement by treatment of mice with cobra venom factor blocked reticuloendothelial system clearance and resulted in fatal infection in both diabetic and control mice. These results indicate that neither type-specific antibody nor an intact complement system is adequate for effective clearance of type II GBS bacteremia in mice with experimentally induced diabetes. This clearance deficit could be the result of a defect in hepatocyte membrane receptors necessary for removal of this encapsulated microorganism.

Bacterial Translocation from the Gastrointestinal Tract in Various Mouse Models for Human Diabetes

“…Thus, immunological differences between NOD mice and ICR mice may also influence bacterial translocation from the GI tract to the MLN. In in vivo studies, diabetic animals have shown an increased susceptibility to bacterial infections due to various impaired host defense mechanisms (4,7,13). Same researchers reported, in contrast, that diabetic animals did not always have increased susceptibility to bacterial infections (3,8).…”

GM-CSF Administration Improves Defects in Innate Immunity and Sepsis Survival in Obese Diabetic Mice

“…Successful neutrophil infiltration promotes effective monocyte influx that orchestrates and optimizes innate and adaptive immune interplay. Although a few researchers have shown that obese, diabetic mice have defective neutrophil function and poor survival after sepsis (30,31), there are few studies that focus on neutrophil dysregulation and the effects on innate immune responses.…”

“…Animal models of sepsis demonstrate that obese, diabetic mice have much lower survival rates compared with nondiabetic mice (30,31). We have shown in sepsis that neutrophils are essential for eradication of bacteria, prevention of infectious complications, and sepsis survival (32).…”

The association of admission hyperglycaemia and adverse clinical outcome in medical emergencies: the multinational, prospective, observational TRIAGE study

“…Diabetes also affects the adaptive immune system, with impaired T‐cell function and decreased antibody production . In animal models, hyperglycaemia is associated with decreased bacterial clearance and increased mortality in bacteraemia .…”