The Interplay between Immune Cells and Staphylococcus aureus in Kidney Infections

葡萄球菌（S.）金黄色葡萄球菌是一种细菌，其主要定殖于约30%的健康人群的皮肤和粘膜，但可引起例如皮肤的一些感染，这在正常条件下可容易地由免疫系统控制。虽然S.金黄色葡萄球菌可引起严重的危及生命的全身感染，通常是由于作为导管的血管进入装置或皮肤脓肿破裂。此外，这种细菌对抗生素的耐药性越来越强，导致患者的治疗更加困难。系统性S.金黄色葡萄球菌感染导致器官衰竭，肾脏通常受到影响。肾脏是一个非常重要的器官，由不同的解剖结构组成，具有不同的细胞类型，以维持例如排泄废物的功能，这在感染期间可能会受到影响。但是在S.金黄色葡萄球菌感染以及如何进入肾脏的细菌是完全未知的。吞噬细胞-中性粒细胞和单核细胞/巨噬细胞-主要是免疫系统中消除细菌的第一批细胞。因此，研究这些细胞与S.金黄色葡萄球菌及其在病原体向肾脏传播中的作用。系统性S.在金黄色葡萄球菌感染中，大多数细菌被肝脏巨噬细胞捕获和清除，然而，大约10%能够克服这种免疫机制并传播到其他器官，特别是肾脏。一种可能性是，一旦细菌从肝脏巨噬细胞中逃脱，它们就被中性粒细胞识别，并通过血液在这些细胞中以特洛伊木马的形式转运到其他器官。腹膜腔中的巨噬细胞是一种可以浸润内脏器官的细胞类型，是S.金黄色葡萄球菌的肾脏，因为我的初步数据显示，在系统性S。金黄色葡萄球菌感染的细菌也生长在腹膜腔。金黄色葡萄球菌传播到肾脏，并且中性粒细胞和巨噬细胞在此过程中发挥作用。已经建立的系统性S.金黄色葡萄球菌感染与2-光子活体显微术的组合将在体内显示细菌在什么时间点到达肾脏的哪个区域。不同的报告基因或敲除小鼠将提供关于免疫细胞贡献的信息。本研究将为系统性和肾性S.金黄色葡萄球菌感染，并确定传播机制的肾脏，构成了免疫过程的调节，导致新的治疗选择的基础。重要的是要了解金黄色葡萄球菌肾脏感染是如何发生的，以开发可以阻止这一过程并挽救患者器官衰竭的药物。

Staphylococcus (S.) aureus is a bacterium that colonizes mostly the skin and mucosae of around 30 % of the healthy population but can cause some infection for example of the skin, which can easily be managed by the immune system under normal conditions. Albeit, S. aureus can cause severe life-threatening systemic infections often due to vascular access devices as catheters or rupture of skin abscesses. Additionally, the bacterium is developing more and more resistance against antibiotics resulting in more difficulties in patients´ treatment. Frequently, systemic S. aureus infectious result in organ failure and the kidneys are commonly affected. The kidney is a very important organ that is comprised of different anatomical structures with different cell types to maintain functions as e.g. the excretion of waste, which can be affected during infections. But which part of the kidneys and which cells are affected in S. aureus infections as well as how the bacteria entering the kidneys is completely unknow. Phagocytes – neutrophils and monocytes/macrophages – are mainly the first cells of the immune systems that eliminate bacteria. Therefore, it is of great interest to investigate the interplay between these cells with S. aureus and their role in dissemination of the pathogen to the kidneys in more detail. During systemic S. aureus infections, most bacteria are getting caught and eliminated by liver macrophages, however, around 10 % are able to overcome that immune mechanism and spread to other organs, especially the kidneys. One possibility is that as soon as the bacteria escape from liver macrophages they are recognized by neutrophils and transported in these cells in a Trojan Horse via the blood stream to other organs. Macrophages in the peritoneal cavity, a cell type that can infiltrate inner organs, present a second possibility for dissemination of S. aureus to the kidneys, as my preliminary data show that in systemic S. aureus infections the bacteria also grow in the peritoneal cavity.The main aim of this proposal is to investigate how S. aureus disseminates to the kidneys and which role neutrophils and macrophages play in this process. An already established mouse model of systemic S. aureus infection in combination with 2-photon intravital microscopy will show in vivo at what time point bacteria arrive in which areas of the kidneys. Different reporter or knock out mice will provide information about the contribution of immune cells. This project will provide new insights into the pathogenesis of systemic and renal S. aureus infections and identify dissemination mechanisms to the kidney that constitute a basis for modulation of immunological processes leading to new options for therapy. It is important to understand how Staphylococcus aureus kidney infections occurs to develop drugs that can prevent this process and save patients from organ failure.