Host-Pathogen Dialogues in Autophagy, Apoptosis, and Necrosis during Mycobacterial Infection.

Abstract

Mycobacterium tuberculosis (Mtb) is an etiologic pathogen of human tuberculosis (TB), a serious infectious disease with high morbidity and mortality. In addition, the threat of drug resistance in anti-TB therapy is of global concern. Despite this, it remains urgent to research for understanding the molecular nature of dynamic interactions between host and pathogens during TB infection. While Mtb evasion from phagolysosomal acidification is a well-known virulence mechanism, the molecular events to promote intracellular parasitism remains elusive. To combat intracellular Mtb infection, several defensive processes, including autophagy and apoptosis, are activated. In addition, Mtb-ingested phagocytes trigger inflammation, and undergo necrotic cell death, potentially harmful responses in case of uncontrolled pathological condition. In this review, we focus on Mtb evasion from phagosomal acidification, and Mtb interaction with host autophagy, apoptosis, and necrosis. Elucidation of the molecular dialogue will shed light on Mtb pathogenesis, host defense, and development of new paradigms of therapeutics.