MHC-II abhängige Aktivierung von T-Zellen durch das zwitterionische Zellwandpolymer Wandteichonsäure von Staphylococcus aureus
Final Report Abstract
Staphylococcus aureus attracted strong interest recently due to the emerge of severe skin and soft-tissue infections (SSTIs) caused by community-acquired methicillin-resistant isolates. However it is still unclear which factors of S. aureus are important in SSTIs. This project led to the discovery that a zwitterionic cell wall polymer of S. aureus, the cell wall teichoic acid (WTA) plays a major role in skin abscess formation. WTA composes a major part of the staphylococcal cell wall and has a zwitterionic structure. In this project we were able to demonstrate that WTA is able to activate CD4 T cells by being presented on the MHCII molecules of antigen presenting cells (APCs). WTA presentation on MHCII depends on the zwitterionic charge of the polymer and follows the intracellular MHCII presentation pathway as described for peptide antigens and other zwitterionic polysaccharides like PSA of Bacteroides fragiles. WTA was able to induce lesions in a subcutaneous mouse model of abscess formation. This abscess formation was strongly modulated by the ability of WTA to activate CD4 T cells. These findings link recent insights into carbohydrate immunology to the complex pathology of skin and soft tissue infections caused by S. aureus. This project sheds a new light on the zwitterionic cell wall polymer WTA as an MHC II dependent antigen and implies the idea that WTA could be useful as part of an anti staphylococcal vaccine. In addition the project opens new opportunities for multiple new projects that will be part of the applicant’s scientific future. It is of great interest to elucidate the relative content of WTA in clinical isolates of S. aureus to understand the impact of WTA when compared to other factors. Furthermore it will be interesting to compare structurally different WTA polymers of other gram positive pathogens for their immune modulatory activity. The molecular mechanisms that link T cells and skin infections during a S. aureus infection will also be a focus of future projects. These findings might have direct impact on the treatment or prevention of S. aureus infections and will be therefore of public interest.
