P18

The disability of our immune system to ultimately clear a Mycobacterium tuberculosis (Mtb) infection is one of the main reasons why 1/4 of the world population is considered latently infected and thus, at risk to develop active tuberculosis. One putative key-element responsible was initially reported by Tornack et al. in 2017. They observed that M. tuberculosis (Mtb) not only infects mature innate immune cells of myeloid origin but also the ultimate immune cell source: hematopoietic stem cells (HSC). However, cellular and molecular interactions between Mtb and HSCs and their implications for downstream immunity and pathogenesis remain obscure.

To characterize the impact of Mtb on the functionality and the downstream fate of HSC and their successors, we designed a protocol to isolate a homogenous population of live and infected HSC which was confirmed by confocal microscopy. In addition, we characterised mechanisms turning otherwise uninfectable cells to those susceptible to Mtb. We could show that HSC get infected in an active and actin-dependent process that seems to be triggered during the interaction with Mtb. We could also show that to become permissive for Mtb, HSC require triggering signals generated by metabolically active mycobacteria such as microbial metabolites and likely does not involve PAMPs. Connecting the established methods for HSC purification and tracking with the available in vitro systems each comprising different unique traits will allow us to more detailly understand the interactions between HSCs and Mtb.