Impact of autologous serum on an in vitro granuloma model to study Mycobacterium tuberculosis infection dynamics

Tuberculosis (TB) remains a global health challenge, with Mycobacterium tuberculosis (Mtb) persisting in granulomas, complex immune structures that balance containment and survival of the pathogen. In vitro granuloma models have advanced TB research but often rely on commercial human serum, which may not fully replicate the native immune environment. Here, we investigated the role of autologous serum, either heat-inactivated or native, in granuloma-like structure (GLS) formation, bacterial dynamics, and immune responses. Using a human PBMC-based model to induce spontaneous in vitro granuloma formation after infection with Mtb, we found that autologous serum significantly enhanced GLS formation and altered cytokine profiles compared to commercial serum. Native serum also reduced bacterial growth, likely due to active complement system-mediated immune responses. These findings highlight the importance of autologous serum in creating physiologically relevant models, crucial for preclinical evaluation of TB therapies. Incorporating patient-specific serum can improve model accuracy, enabling better exploration of host-pathogen interactions and targeted therapeutic strategies.