Intelligent Mechanisms of Macrophage Apoptosis Subversion by Mycobacterium

Abstract

Macrophages are one of the first innate defense barriers and play an indispensable role in communication between innate and adaptive immune responses, leading to restricted Mycobacterium tuberculosis (Mtb) infection. The macrophages can undergo programmed cell death (apoptosis), which is a crucial step to limit the intracellular growth of bacilli by liberating them into extracellular milieu in the form of apoptotic bodies. These bodies can be taken up by the macrophages for the further degradation of bacilli or by the dendritic cells, thereby leading to the activation of T lymphocytes. However, Mtb has the ability to interplay with complex signaling networks to subvert macrophage apoptosis. Here, we describe the intelligent strategies of Mtb inhibition of macrophages apoptosis. This review provides a platform for the future study of unrevealed Mtb anti-apoptotic mechanisms and the design of therapeutic interventions.

Small RNA sequencing and bioinformatics analysis of RAW264.7-derived exosomes after Mycobacterium Bovis Bacillus Calmette-Guérin infection

“…Moreover, Mtb has evolved a series of intelligent strategies to hijack host cell miRNAs to subvert the abovementioned functions and achieve immune evasion [ 3 ]. Numerous emerging studies have revealed that miRNAs can manipulate host macrophage defence against Mtb infection [ 4 , 5 ], but a detailed and comprehensive understanding of the mechanisms remains unclear.…”

Resistance and Susceptibility Immune Factors at Play during Mycobacterium tuberculosis Infection of Macrophages

“…Apoptosis, or programmed cell death, is an important host defense mechanism against infection as it can promote pathogen clearance and resolution of inflammation [ 73 ]. M.tb has evolved various strategies for inhibition of apoptosis, ranging from the inhibition of calcium influx, suppressing cell death pathways, or promoting the expression of anti-apoptotic factors [ 74 , 75 ]. Our lab recently identified one such mechanism, in which M.tb induces the expression of the peroxisome proliferator-activated receptor (PPAR)γ in human MDMs, which in turn drives the expression of Mcl-1, a pro-survival member of the Bcl-2 family.…”

Mycobacterium tuberculosis Pathogenesis, Infection Prevention and Treatment

“…Concerning the macrophages reprogramming capability, Abdalla A.E. and co-authors contribute to the Special Issue with a review discussing the multiple mechanisms adopted by MTB to interfere with macrophage apoptosis [26]. In particular, they describe the anti-apoptotic determinants, listing the mechanism of action and the main molecular outcome.…”