Trained immunity within the mononuclear phagocyte (precursor) pool and its role for immune responses to unrelated pathogens after vaccination
There is strong evidence for long-lasting changes within the innate immune system triggered by different immunological and non-immunological stimuli, such as vaccines. These include a changed induction of responses not only to the same, but also to heterologous, so far not seen pathogens and is often termed ‘trained immunity’. We here hypothesize that different immune stimuli (e.g., vaccinations, TLR ligands, or infections) induce long-term changes in hematopoietic progenitors shaping the innate immune cell pool and that the history of immunological challenges influences the immune reactions to heterologous challenges. To test our hypothesis, we aim to:
- Determine the presence, number, frequencies, and phenotype of hematopoietic DC-precursor pool and their progeny (steady state);
- Analyze the differentiation of hematopoietic DC-precursors in vitro and upon cell transfer (steady state);
- Analyze changes by inducers of trained immunity (e.g., TLR ligands and viral infections) and consequences for subsequent vaccinations
