Interactions of trace elements in modulating the immune response during acute and chronic inflammation in mice
In TraceAge I, we could show that supplying mice with low amounts of the trace elements (TE) Cu, Fe, I, Mn, Se, and Zn (TE-) results in growth retardation and increased spleen weight in comparison to mice with adequate TE intake. In line with splenomegaly, serum levels of the inflammatory mediators TNF-α and CRP were increased. Based on our results, it appears that the immune system is very sensitive towards changes in TE intake. During aging, a low-grade systemic inflammation, called inflammaging, has been described. Thus, it is tempting to speculate that older organisms might have another need for TE to cope with inflammation than younger individuals. To address this, we aim to combine our established TE- regime with models of acute and chronic inflammation in young and old mice by applying the DSS model to induce colitis and LPS injection to study systemic inflammation. Besides TE profiles, inflammatory parameters as well as intestinal integrity will be analyzed. Vice versa, it is well-established that TE homeostasis is regulated in a different manner under conditions of inflammation as part of the so-called nutritional immunity. Thus, we aim to understand, how an acute and chronic inflammation affect the TE status and their biomarkers. Both questions will be addressed in mice and complemented with mechanistic studies conducted in cell culture. This project is supposed to provide the basis for considering all six TE in the future to better characterize and eventually improve the health status of humans suffering from acute and chronic inflammation.