Cell death mechanisms during Mycobacterium tuberculosis infection: A perspective from a host-pathogen interface

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a life threatening disease, which accounts for millions of lives annually. Mtb is an intracellular bacterium, has coevolved with humans to premeditate its machinery to surpass the immunity mounted against it in order to persist for long durations in the system. Cell death is a fundamental process required not only for tissue homeostasis but also for providing protection against intracellular pathogens. Various forms of cell death processes are known including apoptosis, pyroptosis, necroptosis, autophagy etc., that have been shown to play important roles in anti-TB immunity against Mtb. Moreover, inhibition of these pathways by Mtb is considered as one of the virulence mechanisms by which the pathogen is able to survive and replicate inside the host. Apart from identification of newer drug targets and development of anti-TB drugs that solely target the pathogen, recent advancements have been made in developing host-directed therapies against TB, which are aimed at modulating the host responses to reduce excessive inflammation and tissue damage. Thus, understanding the proteins and signaling cascades associated with cell death modalities and their relation with Mtb infection will give us new insights into the area of host-pathogen interactions and help us design better host-directed therapies.

Keywords: Apoptosis; Autophagy; Bacterial infection; Cell death mechanisms; Ferroptosis; Host directed therapies; Mycobacterium tuberculosis; Necroptosis; Pyroptosis.