The role of neural progenitor cells in brain tuberculosis 4691

Description Tuberculosis (TB) of the central nervous system (CNS) is one of the rarest but highly destructive manifestations of Mycobacterium tuberculosis (Mtb) infection in humans. Only half of the patients survive and cognitive diseases are common. The existing knowledge about the infectious mechanisms and anti-mycobacterial immune responses in the brain is restricted by the lack of an optimal human CNS-TB model. In this research, we applied a new human in vitro model to investigate CNS-TB by infecting neural organoids and neural progenitor cells (NPC) with Mtb. Our research reveals that the phagocytic ability of NPCs towards Mtb offers a new perspective on CNS-TB studies. Internalized Mtb bacilli are found co-localized within late endosomal and phagolysosomal compartments, as well as in the cytoplasm of the NPCs. The Mtb infection induces NPC death and disrupts proliferation, further substantiating the pathological consequences of CNS-TB. Additionally, prominent type-1 IFN responses were observed in Mtb-infected NPCs. The treatments with anti-IFN alpha neutralization antibodies could partially rescue the NPCs from Mtb-induced proliferation impairments and cell death. Ultimately our findings demonstrate that these neural organoids and NPC-based in vitro systems offer a new approach for understanding the pathogenesis of CNS-TB and the associated learning deficiencies. Organoid cultures may offer a new platform for evaluating anti-mycobacterial treatment strategies for human CNS-TB.