During bacteremia, phagocytes in spleen and liver form a lympho-hematopoietic interface that monitors and clears the circulation. While phagocytes of the liver function as a “firewall” that effectively remove bacteria from the circulation, induction of long-term anti-infective immunity relies on phagocytic events in the spleen. Full control of systemic Listeria monocytogenes (LM) infection, for example, requires the induction of LM-specific cytotoxic T cell immunity in the spleen, driven by antigen-laden professional antigen presenting cells (APC). The processes at the basis of specific immunity to LM may equally be of relevance for the efficacy of vaccines against infections, allergy or cancer. In this project we aim to unravel how blood borne, cellular, and anatomical factors work in concert to effectively guide adaptive immunity to systemic bacterial infections. It is our aim to use this knowledge in a targeted manner to influence, direct and stimulate effective immunity.

Aims:

1. Dissect the “anatomical route” systemic bacteria take within the splenic immune cell matrix

2. Define the cellular and molecular basis for effective bacterial targeting to splenic APC

3. Boost immune response to systemic bacteria