Modelling human immune response dynamics to Mycobacterium Tuberculosis infection.

[摘要] ENGLISH SUMMARY: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) still poses a great challengeto the well-being of the population, particularly in Sub-Saharan Africa. The abilityto trigger strong mounted cellular response within the host environment is daunting.The host cell depends on the robust adaptive cellular immunity to battle MTB infection.Of these, localizing TB bacteria by the development and the sustainability of a strongT helper type 0 cells (Th0) response is key to thwart MTB dissemination. The factorsfuelling TB pathogenesis include, Human Immunodeficiency Virus (HIV) and TB copandemic,the growing burden of Multidrug-resistant TB (MDR-TB) and Extensive drugresistant TB (XDR-TB), and incompetency of host cell to kill MTB. The survived MTBload can trigger Latent TB infection (LTBI). In addition, the largely unknown biologyof the host-MTB interaction, is yet to be elucidated. In this study, we develop a mathematicalmodel capturing and addressing key dynamics of the adaptive host immuneresponse to MTB infection. Of these, we consider the interplay of MTB with three distinctsubsets of key immune cells and cell signalling molecules, namely; macrophages,T cells and cytokines. Furthermore, we explore the mechanisms of phagocytosis, T cellspriming with delay, macrophage activation leading to lysis of infected cells. To estimateunknown parameters in the model, we perform curve fitting to experimental data of aninfected mice using non-linear least square and Bayesian-based Markov Chain Monte Carlo methods. We use the reproductive number R0, to address factors altering the stabilityof the system. This study provides insight on how the immune system can beamplified to clear the survived intracellular MTB.

[发布机构] Stellenbosch University