Abstract

The WHO objective of eradicating tuberculosis (TB) by 2050 can be achieved by developing more potent anti-TB vaccinations and enhanced preventative medicines against endogenous reactivation of latent TB. What are the factors that lead to a robust memory response after an initial infection? is one of the most important relevant outstanding questions in TB research. ii) How can cytokines contribute to a memory response that is protective against a secondary infection? iii) What are the mechanisms causing the elderly to have a higher risk of reactivation? We looked at a computational model of the immune response to Mycobacterium tuberculosis, which included a mathematical explanation of immunosenescence and the creation and maintenance of immune memory, to try to answer these questions. Key processes governing TB reactivation and immunological memory were identified through the application of sensitivity analysis techniques, thorough model characterization, and in-silico studies. The following model projections sum up the study’s key findings: Tumor Necrosis Factor (TNF) levels during primary infection are associated with increased memory protection strength and duration; production of TNF, but not interferon, by memory T cells during secondary infection is a major factor in effective protection; and impaired CD4+ T cell recruitment may encourage the reactivation of latent TB infections in ageing hosts. In this work, immunosenescence and memory are taken into account in an effort to understand the immunological dynamics of a persistent infection over the course of the host’s lifetime. Even though the model is particular to tuberculosis, the findings are transferable to other persistent bacterial diseases and can help with the creation, assessment, and improvement of TB treatment and/or immunization regimens.