Effect of a high fat diet on pyelonephritis

我们的西方饮食富含脂肪和盐，包括胆固醇，所有这些都深刻地影响免疫反应。国家消费研究II（Nationale Verzehrsstudie II）和NEMONIT研究表明，脂肪在能量摄入中的比例，特别是饱和脂肪酸，高于德国的DGE建议。西方饮食增加了肾脏疾病的发病率。在一项初步研究中，我们观察到实验性肾盂肾炎（PN）模型在接受高脂饮食（HFD）的小鼠中加重。脂肪或肉类消费（富含饱和脂肪酸）对肾脏细菌感染的影响尚未得到系统研究。因此，我们希望实现以下目标：（I）表征HFD对肾内免疫应答和对肾脏、免疫细胞脂质组成和代谢的作用，（II）阐明表达NLRP 3和TREM2的巨噬细胞在HFD抑制的针对PN的防御中的作用，（III）阐明HFD诱导的激素在抑制的针对PN的防御中的作用，以及（IV）研究如何改变脂肪酸质量（饱和脂肪酸与不饱和脂肪酸）可能代表肾脏感染的可能治疗选择。我们的工作将扩展以前的观察西方饮食对PN的抗菌防御的影响，并提供在免疫学背景下改变代谢途径的见解。最后，我们的研究结果可能会影响管理的患者患有这种反复感染的定义支持性饮食措施。

Our Western diet is rich in fat and salt including cholesterol, all of which profoundly influence immune responses. The National Consumption Study II (Nationale Verzehrsstudie II) and the NEMONIT study revealed that the proportion of fat in energy intake, especially saturated fatty acids, is above the DGE-recommendations in Germany. Western diet increases the incidence of kidney diseases. In a preliminary study, we observed that an experimental pyelonephritis (PN) model was aggravated in mice receiving a high fat diet (HFD). The influence of fat or meat consumption (rich in saturated fatty acids) on bacterial infections of the kidney has not yet been systematically investigated. Therefore, we would like to address the following aims: (I) Characterize the effects of a HFD on the intrarenal immune response and on the kidney, immune cell lipid composition and metabolism, (II) Clarify the roles of NLRP3- and TREM2-expressing macrophages in the HFD-suppressed defense against PN, (III) Clarify the role of HFD-induced hormones in the suppressed defense against PN, and (IV) Investigate how changing the fatty acid quality (saturated vs. unsaturated fatty acids) may represent a possible therapeutic option in kidney infection. Our work will extend previous observations on the effects of a Western diet on the antibacterial defense in PN and provide insights into altered metabolic pathways in an immunological context. Finally, our findings may impact the management of patients suffering from such recurring infections by defining supportive dietary measures.