The immune system protects us from communicable diseases. On one hand, adaptive immunity provides a delayed but antigen-dependent, tailored response ultimately generating memory for the reencounter of the same or similar pathogens. On the other hand, innate immunity reacts fast but unspecific only upon encounter of molecular patterns related to tissue damage or pathogens. For a long time, immunological memory was thought to be a unique feature of the adaptive arm of our immune system. However, early childhood vaccinations with BCG (Bacillus Calmette-Guérin), historically used to induce immunity against tuberculosis, have been associated with a better outcome upon infection with even completely unrelated pathogens. In recent years, this was linked to enhanced responses from innate immune cells upon restimulation with unrelated pathogens, due to previous infections or vaccinations. These enhanced responses may depend on epigenetic imprinting, changes in metabolism, surface marker expression and cytokine secretion and have been termed ‘trained immunity’ or ‘innate immune memory’. Trained immunity effects have been observed months to years after the first stimulus, longer than the life span of most innate immune cells, indicating changes in the innate immune cell progenitors.
Therefore, we aim to study the impact of different pattern recognition receptor ligands and vaccine platforms on hematopoietic progenitors, leading to the aforementioned proposed trained immunity characteristics for long-lasting enhanced or diminished immune reactions against unrelated pathogens. We will utilise an in vitro co-culture model to determine the differentiation potential of trained progenitors. Additionally, in vivo mouse experiments will demonstrate how vaccination affects protection against subsequent infection with unrelated pathogens. Therefore, innate immune cells will be analysed for epigenetic and metabolic changes, as well as differences in surface marker expression or cytokine secretion.
The results of this project will benefit current and future vaccine development by understanding the effects of vaccines on the hematopoietic system.
