Modelling the human immune response dynamics during progression from Mycobacterium latent infection to disease

In this paper, we study the immune system’s response to infection with the bacteria Mycobacterium tuberculosis (the causative agent of tuberculosis). The response by the immune system is either global (lymph node, thymus, and blood) or local (at the site of infection). The response by the immune system against tuberculosis (TB) at the site of infection leads to the formation of spherical structures which comprised of cells, bacteria, and effector molecules known as granuloma. We developed a deterministic model capturing the dynamics of the immune system, macrophages, cytokines and bacteria. The hallmark of Mycobacterium tuberculosis (MTB) infection in the early stages requires a strong protective cell-mediated naive T cells differentiation which is characterised by antigen-specific interferon gamma (IFN-γ). The host immune response is believed to be regulated by the interleukin-10 cytokine by playing the critical role of orchestrating the T helper 1 and T helper 2 dominance during disease progression. The basic reproduction number is computed and a stability analysis of the equilibrium points is also performed. Through the computation of the reproduction number, we predict disease progression scenario including the latency state. The occurrence of latent infection is shown to depend on a number of effector function and the bacterial load for R0 < 1. The model predicts that endemically there is no steady state behaviour; rather it depicts the existence of the MTB to be a continuous process progressing over a differing time period. Simulations of the model predict the time at which the activated macrophages overcome the infected macrophages (switching time) and observed that the activation rate (ω) correlates negatively with it. The efficacy of potential host-directed therapies was determined by the use of the model.

Modelling the human immune response dynamics during progression from Mycobacterium latent infection to disease

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Nicholas Opoku

"Modelling the human immune response dynamics during progression from Mycobacterium latent infection to disease"

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