Macrophage Apoptosis in Tuberculosis

Abstract

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that infects alveolar macrophages following aerosol transmission. Lung macrophages provide a critical intracellular niche that is required for Mtb to establish infection in the human host. This parasitic relationship is made possible by the capacity of Mtb to block phagosome maturation following entry into the host macrophage, creating an environment that supports bacillary replication. Apoptosis is increasingly understood to play a role in host defense against intracellular pathogens including viruses, fungi, protozoa and bacteria. In the last 15 years an understanding of the role that macrophage apoptosis plays in TB has begun to emerge. Here we review the history and current state of the art of this topic and we offer a model of the macrophage-pathogen interaction that takes into the account the complexities of programmed cell death and the relationship between various death signaling pathways and host defense in TB.

Notch signaling regulates expression of Mcl-1 and apoptosis in PPD-treated macrophages

“…These bacteria evade the immune response and survive in the host by controlling the type of cell death in infected macrophages. 2,3 While apoptosis of infected macrophages is considered beneficial for controlling bacterial growth and stimulating the adaptive immune response, necrosis of macrophages helps disseminate bacteria. 3,34 Virulent Mycobacterium tuberculosis manipulates host cell death mechanisms by inducing the expression of Mcl-1.…”

“…1 Apoptosis of macrophages is one of the defense mechanisms of the host that eliminates both the infected cells and the bacteria residing inside these cells. 2,3 Furthermore, apoptotic macrophages are critical for inducing adaptive immune responses, as apoptotic vesicles containing mycobacteria are phagocytized by nearby antigen-presenting cells and presented to CD8 1 T cells. 4,5 Apoptosis of macrophages in this setting is partially tumor-necrosis factor-dependent.…”

In vitro infection of human cells with Mycobacterium tuberculosis

“…We have accumulated a large body of knowledge about the immune response to M. tuberculosis, that largely depends on the IL-12-IFNγ axis 6 , but we do not know whether there are immunological mechanisms able to completely eliminate the microorganism and if they exist, which their nature are. There are several candidate processes that may determine eradication or mycobacterial growth restriction, such as reactive oxygen or nitrogen species production 7,8,9 , antimicrobial peptides production 10,11,12 , hydrolytic enzymes and pH regulation 13,11 , apoptosis 14 The importance of NO in the antimycobacterial activity of human cells is less clear but several lines of evidence support the participation of this defence mechanism 9 . In this review I will focus on the analysis of in vitro models of infection that have been devised to study antimycobacterial activity in human cells.…”

IL-32 Is a Host Protective Cytokine against Mycobacterium tuberculosis in Differentiated THP-1 Human Macrophages

“…Apoptosis is becoming well-established as an important killing mechanism for intracellular M. tuberculosis, although the precise means by which it occurs in killing mycobacteria is complex (2). The extrinsic apoptotic pathway is activated by avirulent M. tuberculosis H37Ra to a greater degree than by the more virulent M. tuberculosis H37Rv strain, accounting in part for the lower virulence in the former strain (74).…”

“…Although alveolar macrophages provide a first line of defense against Mycobacterium tuberculosis, macrophages may also provide a safe intracellular niche for mycobacteria if host cells are unable to kill them (2,3). Whether the initial infection leads to complete elimination, a progressive infection, or a state of latent infection ultimately depends on the effectiveness of both the innate immune system and the cellmediated immune system, orchestrated by macrophages and dendritic cells.…”