title: Mathematical model of mycobacterium-host interaction describes physiology of persistence.
abstract: Despite extensive studies on the interactions between Mycobacterium tuberculosis (M.tb) and macrophages, the mechanism by which pathogen evades anti-microbial responses and establishes persistence within the host cell remains unknown. In this study, we developed a four-dimensional ODE model to describe the dynamics of host-pathogen interactions in the early phase of macrophage infection. The aim was to characterize the role of host cellular regulators such as iron and lipids, in addition to the bactericidal effector molecule Nitric Oxide. Conditions for existence and stability of the equilibrium point were analysed by examining the behaviour of the model through numerical simulations. These computational investigations revealed that it was the ability of pathogen to interfere with iron and lipid homeostatic pathways of the host cell, which ensured a shift in balance towards pathogen survival and persistence. Interestingly, small perturbations in this equilibrium triggered the cell's bactericidal response, thereby producing an oscillatory dynamic for disease progression.
authors: International Centre for Genetic Engineering and Biotechnology. Aruna Asaf Ali Marg 110 067, New Delhi, India. Electronic address: gabriele@icgeb.res.in.
authors: Gabriele
authors: G
authors: Pedruzzi
authors: International Centre for Genetic Engineering and Biotechnology. Aruna Asaf Ali Marg 110 067, New Delhi, India; Translational Health Science and Technology Institute, Drug Discovery Research Centre, Plot No. 496, Phase-III, Udyog Vihar, Gurgaon 122016, Haryana, India. Electronic address: kanury@icgeb.res.in.
authors: Kanury V S
authors: KV
authors: Rao
authors: Translational Health Science and Technology Institute, Drug Discovery Research Centre, Plot No. 496, Phase-III, Udyog Vihar, Gurgaon 122016, Haryana, India. Electronic address: samrat.chatterjee@thsti.res.in.
authors: Samrat
authors: S
authors: Chatterjee
mesh_terms: D000818:Animals; D003198:Computer Simulation; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D008264:Macrophages / Q000276:immunology*; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000502:physiology*
keywords: Differential equations; Host–pathogen interaction; Iron; Lipids; Nitric Oxide