Harnessing computational models to uncover the role of the immune system in tuberculosis treatment

The importance of the immune system (IS) in tuberculosis (TB) drug development is often underestimated because of the intricate nature of experiments and the specialized knowledge needed. In vitro and animal studies fall short in replicating the intricate reactions of the human IS to drugs and infections. In this study, we present our initial efforts in employing an in silico approach to comprehend how an individual’s IS impacts the efficacy of therapy, particularly in managing mycobacterium tuberculosis (Mtb) infection and minimizing the risk of relapse. We employed a well-established agent-based IS simulator called C-IMMSIM. We conducted simulations to investigate the long-term outcomes of TB disease in a virtual cohort infected with Mtb over a 50-year period. Our simulations revealed that individuals with competent IS showed a high success rate in containing Mtb infection. Furthermore, to better understand the dynamic interactions between Mtb and the IS, we deliberately introduced specific IS deficiencies, thus successfully inducing short-term relapses and mortality. These results confirm the model’s ability to elucidate the mechanisms underlying the interactions between Mtb and the IS.