Modelling host-Trypanosoma brucei gambiense interactions in vitro using human induced pluripotent stem cell-derived cortical brain organoids

Background: Sleeping sickness is caused by the extracellular parasite Trypanosoma brucei and associated with neuroinflammation neuropsychiatric disorders, including disruption of sleep/wake patterns, now recognised as a circadian disorder. traditionally studied using murine models infection due to lack alternative in vitro systems that fully recapitulate cellular diversity functionality human brain. The aim this study develop much-needed system reduces replaces live animals for infections in central nervous system, sleeping model infection. Methods: We developed co-culture induced pluripotent stem cell (iPSC)-derived cortical brain organoids pathogen T. b. gambiense host-pathogen interactions vitro. Upon co-culture, we analysed transcriptional responses over two time points. Results: detected broad changes exposed gambiense, mainly innate immune responses, chemotaxis, blood vessel differentiation compared untreated organoids. Conclusions: Our provides novel, more ethical avenues experimental mice. Future work required increase complexity (e.g., addition microglia vasculature). We envision adoption organoid will be beneficial researchers studying mechanisms protozoan parasites. Furthermore, have potential used other parasites affect brain, neurocysticercosis, significantly reducing number undergoing moderate and/or severe protocols infections.