Autologous host-pathogen pairing enhances early immune responses and bacterial growth control in tuberculosis in vitro granuloma model

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health challenge, characterized by significant heterogeneity in its clinical presentation and physiopathology, underscoring the need for optimized models to better understand host-pathogen interactions. This study evaluated the impact of both host and Mtb clinical isolate variability on bacterial growth and dormancy and immune responses using an in vitro granuloma model. Peripheral blood mononuclear cells from active TB patients were infected with autologous and heterologous Mtb clinical isolates, as well as the H37Rv Mtb reference strain. Bacterial growth and dormancy dynamics and cytokines release were assessed at 0-, 7-, 14- and 21-days post-infection. Results revealed that bacterial growth and dormancy dynamics were mostly isolate-dependent, with almost no impact of PBMC donor. However, at 7-days post-infection, autologous infections exhibited lower bacterial loads and elevated Th1-type cytokines, such as TNF-α and IFN-γ. Yet, this early advantage in bacterial control did not persist at later time points. These findings highlight the importance of host-pathogen pairing in shaping immune responses and validate the in vitro granuloma model as a relevant tool for studying TB pathogenesis and evaluating therapeutic interventions. Furthermore, further research is needed to decipher the specificities of autologous immune response.