Glycoproteomic phenotyping and functional analysis of monocytes in different clinical settings of Staphylococcus aureus - induced sepsis
The Staphylococcus aureus-associated disease conditions
- S. aureus Bacteremia with acute sepsis,
- Sustained high mortality in survivors of a S. aureus bacteremia with sepsis and
- Chronic spondylodiscitis / vertebral osteomyelitis after haematogenic spread of the pathogen
are associated with a so-called immunosuppression, occuring due to altered receptor expression patterns and the development of tolerance in the monocyte / macrophage population. Recent developments in mass spectrometry-based technologies enable global qualitative and quantitative analysis of membrane proteins, such as the "surfaceome", comprising all membrane proteins expressed on the cellular plasmamembrane.
Figure: Current coverage of the immunological surfaceome. At least 2383 proteins are estimated from current UniProt annotation to constitute the surfaceome of immune cells. The cluster of differentiation (CD) classifies antigens on the surface of leucocytes. Human CD antigens are currently numbered up to CD360 (Bock et al, 2012).
We are aiming to characterize the secondary immunosuppressive state, occuring after S. aureus bacteremia with sepsis, using a glycoprotein approach for immunophenotyping of monocytic cell surface in different mouse models. The mouse models represent various disease states and clinical symptoms of S. aureus infections. The generated "surfaceome" data will be compared with data from functional analyzes that address the immunological status of the monocytes during the course of a S. aureus infection, with a special focus on S. aureus induced tolerance. In addition, we will compare the results from the mouse experiments with results from the "surfaceome" analysis and functional immunophenotyping of monocytes from patients at various clinical stages of a systemic S. aureus infection.
Our study will identify surface markers of monocytes that allow to describe the patient's immune status during S. aureus bacteremia with sepsis and thus, help to identify functional consequences of monocytic immunosuppression. In addition, the experimental approach allows to identify patient groups that may benefit from immunomodulatory therapies. To sum up, we want to contribute to the role, severity and mechanism of immunosuppression in the course of acute and chronic S. aureus infections.