Investigating vaccine-induced immunity towards tissue-resident memory protecting against pulmonary TB
The main objective of the project is to investigate both adaptive and innate host response cascades ensuing from standard and alternative vaccination strategies. We will use banked and/or fresh materials from non-human primates (NHP) after vaccination and infectious challenge, and over a range from protected to non-protected animals for relevant contrast in TB infection and disease phenotypes. We will primarily deploy spectral cytometry-based immunophenotyping and wherever possible multiplexed (or OMICs-based) immune measurements. Through ex vivo and in vitro cell co-culture experiments the role of monocyte-derived antigen presenting cells (Mo.APC) in activating TRM shall be explored. Towards understanding innate and adaptive crosstalk mechanisms, we shall address functional relationships between T cells and their costimulatory/inhibitory signaling receptors (of the TNF(R)superfamily) versus functionally differentiated Mo.APC, either or not under the influence of antibodies and their macrophage-modulating potential via FcR-mediated signaling. This project will enable cross-cutting activities and leveraging of other BPRC research lines with regard to pulmonary immunity or targeting tissue-specific memory by vaccination in infectious diseases other than TB, as well as monocyte/macrophage-mediated immune regulation in inflammatory diseases.
Contact
Marloes Rietveld