P21

Mycobacterial infections lead to epigenetic reprogramming of host cells. These can be beneficial for the host, as seen in BCG vaccination leading to trained immunity. However, Mycobacterium tuberculosis infection can lead to detrimental modifications of host cells, resulting in immune exhaustion. Chemical histone modifications, such as tri-methylation at certain lysine residues of histone H3, seem to be important mechanisms to reprogram host cells.

In our study, we aim to identify histone modifications in host cells in an experimental model mimicking early-stage MTBC infection. Therefore, we infect human monocyte-derived macrophages with representative MTBC strains and identify changes in certain histone modifications by chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq). In ChIP, histone modifications are bound by specific antibodies and immunoprecipitated together with bound DNA fragments. Our project is focused on the establishment of a ChIP-seq protocol adapted to BSL3 pathogens. One of our major challenges lies in preserving epitope integrity while ensuring the sterility of BSL3 samples.

Eventually, ChIP-seq performed with cells infected with live MTBC will help to answer several open questions in host-pathogen interaction during tuberculosis, including the identification of potential susceptibility factors. Furthermore, it will contribute to understanding the epigenetic reprogramming induced by these pathogens.