1735-P: Oral Exposure to Air Pollutants Mediates Diabetes via Innate Immunity

Background: Besides classical risk factors such as sedentary lifestyle and unhealthy diet, air pollution has emerged as an unexpected risk factor for type 2 diabetes. However, the causal mechanism remains poorly understood. Air pollution particles are known to reach the gastrointestinal tract by mucociliary clearance. Underlining the clinical relevance of oral exposure, air pollution has been associated with a variety of gastrointestinal diseases. Therefore, we aim to study the effects of oral air pollution exposure on glucose metabolism and a potential immune-mediated mechanism.

Research Design and Method: Male C57B6/N, Rag2-/- and CCR2-/- mice or mice on a diet supplemented with a Csfr1-inhibitor were exposed to diesel exhaust particles (DEP; 12µg 5 days/week) or PBS by gavage for up to 6 months. Glycemia, tissue inflammation and immune cells were assessed.

Results: Mice orally treated with DEP developed impaired glucose tolerance with reduced insulin secretion, while insulin resistance, systemic, adipose tissue and liver inflammation were not induced. This effect was independent of the adaptive immunity as Rag2-/- mice, which are devoid of B and T cells, also became glucose intolerant. In contrast, glucose intolerance did not develop in CCR2-/- mice and mice treated with a Csfr1-inhibitor. Supporting a causative role of intestinal macrophages in air pollution-induced diabetes, wild type mice exposed to oral DEP had reduced anti-inflammatory, resident macrophages in the lamina propria of the gut.

Conclusion: Oral exposure to air pollutants results in impaired glucose tolerance, which is mediated by innate immunity as we found a loss of anti-inflammatory, resident macrophages in the gut. Moreover, mice devoid of macrophages are protected from air pollution-induced diabetes. Our findings provide a new understanding how environmental pollutants affect metabolic health, which is crucial for preventing the worldwide disease burden of air pollution-induced diabetes.