Dietary lipids accumulate in mesenteric lymph node cells and influence oral tolerance induction
STREICH K. 1, KLEIN M. 1, HEGERMANN J. 1, BLEICH A. 1, BÜTTNER M. 1
1 Hannover Medical School, Hannover, Germany
Obesity increases the risk of various diseases, such as diabetes mellitus type 2 and cardiovascular diseases, but also affects the immune system. During obesity, more dietary fats are absorbed and transported into the bloodstream via the lymphatic systems. Increased fat accumulation leads to impaired lymphatic fluid and atrophy of the mesenteric lymph nodes (mLN). In these secondary lymphoid organs, the lymph fluid is filtered, immune reactions against pathogens are generated or tolerance to harmless antigens is induced. However, the alteration of these functions in the mLN in obesity is still poorly understood. In this study, the changes in the microarchitecture of the mLN during high fat transport were investigated and the induction of oral tolerance was assessed.
To this end, the effects of diet-induced obesity (DIO) on the mLN were investigated in C57BL/6NCrl mice. Mice were fed a high-fat (HFD) or low-fat (LFD) diet for a maximum period of 14 weeks. After 10 weeks of feeding, the lymph node architecture was analysed and oral tolerance was induced.
Lipid droplets were observed in lymphatic endothelial cells, various reticulum cells and macrophages by transmission electron microscopy, and the size of lipid droplets as well as their number and intercellular spacing increased after 10 weeks of high-fat diet.
After oral tolerance induction, we observed an impaired delayed hypersensitivity response (DTH) during DIO, but this was reversible after switching to standard chow. Furthermore, an influence of the lymph node microenvironment on the development of oral tolerance during DIO was detected, with oral tolerance induced in transplanted peripheral lymph nodes.
The results suggest that changes in microarchitecture and increased accumulation of lipid droplets in stromal cells and macrophages influence the immunological function of mLNs.