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

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 $R_0$ is calculated, and criteria on the locally and globally asymptotic stability of infection-free equilibrium $E_0$ are established if $R_0<1$. Criteria on the existence and locally asymptotic stability of immune-free infection equilibrium $\overline{E}$ and immune-activated infection equilibrium $E^{\ast }$ are further obtained if $R_0>1$. Moreover, the model exhibits forward, backward and saddle-node bifurcations at $\overline{E}$, as well as Hopf bifurcation and chaotic dynamics at $E^{\ast }$, 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 ${\gamma }_1$ and ${\gamma }_2$ 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.