Modelling the role of macrophage polarization during pulmonary infection of Mycobacterium tuberculosis with cellular immunity.

Abstract

This paper proposes a within-host Mycobacterium tuberculosis (Mtb) infection model integrating M1/M2 macrophage conversion to explore macrophage polarization regulation in pulmonary infection with cellular immunity. The basic reproduction number R0 is calculated, and criteria on the locally and globally asymptotic stability of infection-free equilibrium E0 are established if R0<1. Criteria on the existence and locally asymptotic stability of immune-free infection equilibrium E¯ and immune-activated infection equilibrium E∗ are further obtained if R0>1. Moreover, the model exhibits forward, backward and saddle-node bifurcations at E¯, as well as Hopf bifurcation and chaotic dynamics at E∗, indicating that Mtb infection is highly sensitive to the dynamic shifts during macrophage polarization. Numerical simulations verify theoretical results, revealing that the effective conversion rates γ1 and γ2 between M1 and M2 macrophages are key regulators of Mtb infection progression, which may provide theoretical insights into tuberculosis latency and relapse, and offer testable predictions for immunotherapeutic strategies.