Orchestration of Host-Pathogen Interaction: Relevance of Iron in Generation of Potent Anti-M. tuberculosis Immunity

Abstract

Pathogenesis of tuberculosis is marked with infection of macrophages followed by expansion of M. tuberculosis. Every step of this host-pathogen interaction is determined by the battle between the pathogen and host immune factors. It starts with phagocytosis of bacilli by mononuclear cells including alveolar macrophages and Dendritic Cells (DCs), both of which are Antigen Presenting Cells (APCs). Phagocytosed M. tuberculosis is subject to degradation by various means inside the phagolysosome. This very specific anti-M. tuberculosis mechanism within the phagocytes is well orchestrated. Upon activation, macrophages exhibit elevated levels of various intermediates via the oxidative burst, which effectively kills the pathogen and inhibits its dissemination. Generation of these intermediates and then their neutralization is intricately linked with the balance of divalent and trivalent iron metals in and outside of the cell. This review will bring the insight of host-M. tuberculosis interaction and its effectiveness in containment of the disease. Furthermore, the physiological balance of iron, its pathogen driven perturbance as well as its effect on the disease will also be discussed.