Mathematical analysis of macrophage-bacteria interaction in tuberculosis infection

Abstract

Tuberculosis (TB) is a leading cause of death from infectious disease. TB is caused mainly by a bacterium called Mycobacterium tuberculosis which often initiates in the respiratory tract. The interaction of macrophages and T cells plays an important role in the immune response during TB infection. Recent experimental results support that active TB infection may be induced by the dysfunction of Treg cell regulation that provides a balance between anti-TB T cell responses and pathology. To better understand the dynamics of TB infection and Treg cell regulation, we build a mathematical model using a system of differential equations that qualitatively and quantitatively characterizes the dynamics of macrophages, Th1 and Treg cells during TB infection. For sufficiently analyzing the interaction between immune response and bacterial infection, we separate our model into several simple subsystems for further steady state and stability studies. Using this system, we explore the conditions of parameters for three situations, recovery, latent disease and active disease, during TB infection. Our numerical simulations support that Th1 cells and Treg cells play critical roles in TB infection: Th1 cells inhibit the number of infected macrophages to reduce the chance of active disease; Treg cell regulation reduces the immune response to stabilize the dynamics of the system.