The Interplay between Immune Cells and Staphylococcus aureus in Kidney Infections

• Applicant: Dr. Selina Kathleen Jorch
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Immunology
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 390018950

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.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Professor Dr. Paul Kubes, Ph.D.