Computational Modeling Predicts IL-10 Control of Lesion Sterilization by Balancing Early Host Immunity–Mediated Antimicrobial Responses with Caseation during Mycobacterium tuberculosis Infection

摘要: Although almost a third of the world’s population is infected with bacterial pathogen Mycobacterium tuberculosis , our understanding functions many immune factors involved in fighting infection limited. Determining role immunosuppressive cytokine IL-10 at level granuloma has proven difficult because lesional heterogeneity and limitations animal models. In this study, we take an silico approach and, through series virtual experiments, predict several novel roles for granulomas: 1) decreased levels lead to increased numbers sterile lesions, but cost early caseation; 2) small increases antimicrobial activity cause lesion sterility; 3) produced by activated macrophages major mediator host-induced 4) increasing macrophage derived promotes persistence limiting response preventing sterilization. Our findings, currently only accessible using approach, suggest that individual scale critical regulator outcome. These predictions IL-10–related mechanisms could be used as adjunctive therapies during tuberculosis.