Cell death and autophagy in tuberculosis

Abstract

Mycobacterium tuberculosis has succeeded in infecting one third of the human race though inhibition or evasion of innate and adaptive immunity. The pathogen is a facultative intracellular parasite that uses the niche provided by mononuclear phagocytes for its advantage. Complex interactions determine whether the bacillus will or will not be delivered to acidified lysosomes, whether the host phagocyte will survive infection or die, and whether the timing and mode of cell death works to the advantage of the host or the pathogen. Here we discuss cell death and autophagy in TB. These fundamental processes of cell biology feature in all aspects of TB pathogenesis and may be exploited to the treatment or prevention of TB disease.

Metformin induced autophagy in diabetes mellitus – Tuberculosis co-infection patients: A case study

“…Several studies related to the autophagy in TB infection, suggest that SOD and IFN-g play important role in autophagy 21,25,31,32 and the results of this study support those information.…”

“…M. tuberculosis has capacity to evade the autophagy of mononuclear phagocytes (MPs) and leverage the intracellular environment as a replication niche. 20,21 Combined with hyperglycemia state and high free radicals of oxygen or nitrogen, infected MPs of DM patients are faced with a pathogen surviving in phagosomes that fail to incorporate the molecular machinery and also fail to fuse with lysosomes to expose bacilli, then, resulting the failure of anti-TB therapy . 22,23 Autophagy in TB infection is a combined response of innate and adaptive host immune systems that are essential for the process of M. tuberculosis elimination.…”

“…29,30 Moreover, IFN-g plays important key in autophagy. 21,30 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 i n d i a n j o u r n a l o f t u b e r c u l o s i s x x x ( 2 0 1 8 ) x x x -x x x Table 5 shows that IFN-g level before treatment between MET group and non MET group were alike ( p > 0.005), thus it shows that patients in both groups, before treatment, were in similar stage of IFN-g. The differences before and after observation period was significant in MET group (p < 0.005) while in non MET group was not.…”

NAD+ Depletion Triggers Macrophage Necroptosis, a Cell Death Pathway Exploited by Mycobacterium tuberculosis

“…However, it is unclear which mechanisms Mtb uses to alter host cell death modes in its favor (Moraco and Kornfeld, 2014). In this study, we demonstrated that the Mtb toxin TNT damages mitochondria, a key event in the necrotic cell death of Mtb-infected macrophages (Chen et al, 2006; Duan et al, 2002; Jamwal et al, 2013).…”

Bacillary replication and macrophage necrosis are determinants of neutrophil recruitment in tuberculosis

“…Macrophage infection with M. tuberculosis has been linked to a diverse range of apoptotic and necrotic cell death modes, based mostly on evidence from in vitro experiments [15]. Macrophages may respond to attenuated mycobacterial strains, including H37Ra, by undergoing caspase-mediated apoptosis that might provide host-protective effects [16,17].…”