The aim of my project is to explore whether epigenetically reprogrammed immunity can explain why some individuals are able to control or eliminate tuberculosis. The phenomenon that we are exploring is known as trained immunity and involves altered DNA methylation patterns and modification of histone proteins. We have shown that trained immune cells display an improved capacity to eliminate pathogens, including Mycobacterium tuberculosis that causes tuberculosis.
Within the frame of this project we collect unique mycobacteria-exposed biological materials, ranging from blood cells of individuals vaccinated against tuberculosis to lung immune cells coughed up by tuberculosis patients. We are taking a genome-wide approach to identify patterns in exposed individuals that reflect protection. Further, we are using our models to identify immune-training agents that effectively mimic mycobacteria-specific trained immunity and test them for efficacy agains M. tuberculosis infection.
Understanding the mechanisms behind natural tuberculosis protection would be a major scientific breakthrough that can be implemented to prevent tuberculosis and other infectious diseases, for which a classical vaccine approach has proven ineffective. In an era in which established tools such as antibiotics are gradually becoming ineffective, this project is breaking new ground in the field of infectious disease control.