Glycolipid-sensing by Natural Killer T cells Group Freigang Natural killer T (NKT) cells are innate-like T cells with powerful immunoregulatory functions that recognize self and microbial glycolipids presented by CD1d molecules. While the efficacy of NKT cell agonists is currently explored in the immunotherapy of infectious diseases and cancer, the mechanisms that control CD1d antigen presentation and NKT cell activation in vivo still remain incompletely understood. This project characterizes pathways linking CD1d antigen presentation to lipid metabolism, and aims to define critical effector functions of NKT cells in microbial infections.
Mechanisms of metabolic adaptation in vascular immunopathology Group Freigang Atherosclerosis-related diseases remain the leading cause of mortality worldwide; and chronic inflammation represents a major driver of disease progression. First clinical trials demonstrated the beneficial effects of anti-inflammatory therapies in CVD patients, a better understanding of the molecular mechanisms of vascular inflammation is required to develop more effective treatment strategies. In this project we investigate how dyslipidemia and the resulting lipid metabolism perturbation in immune cells affects physiological immune responses and contribute to vascular immunopathology in atherosclerosis. En face preparations of the mouse aorta. The atherosclerotic lesions induced by feeding a high fat diet were revealed by staining with Oil Red O
Cell-type specific regulation of IL-1-driven inflammation Group Freigang Invasive fungal infections have high mortality rates with limited therapeutic options. We recently identified macrophage-secreted IL-1 receptor antagonist (IL- 1Ra) as an innate immune checkpoint that facilitates fungal dissemination and candidiasis pathology. We showed that therapeutic IL-1Ra neutralization protects against lethal Candida sepsis, whereas interferon-driven amplification of IL-1Ra during viral infections exacerbates fungal disease. This project explores IL-1/IFN I crosstalk mechanisms, particularly IL-1Ra, as potential biomarkers and therapeutic targets in microbial infection. Immunofluorescence staining of an infected mouse kidney. The tissue dissemination of the fungus Candida albicans was visualized by staining of the fungal cell wall.
