Skip to main content
. 2022 Oct 3;323(5):C1444–C1474. doi: 10.1152/ajpcell.00246.2022

Table 2.

List of Mtb factors associated with host cell death

Actions on host Mtb Protein/Factor Remarks Cell Type Reference
Apoptosis inducers Lipomannan (LM); lipoarabinomannan (LAM); mannosylated lipoarabinomannan (manLAM) Induces apoptosis and IL-12 secretion Human THP-1 (47)
Glycolipoprotein (p19; LpqH) Induces apoptosis through TLR-2 and mitochondrial apoptosis-inducing factor THP-1/CHO expressing TLR2 (48)
Mycolactone Causes apoptosis in guinea pig ulcers and tissue culture cells macrophage cells J774A.1/guinea pig model (49)
Periplasmic phosphate-specific transporter; 38-kDa lipoprotein (Pst-S1) Causes TNF-α and FasL-mediated caspase-dependent apoptosis and upregulation of cell-death receptors TNFR1, TNFR2, and Fas and TLR2 THP-1 macrophages (50)
Early Secreting Antigen Target-6kDa (ESAT-6)-family (esxA, esxT and esxL) Induces apoptosis through activation of caspase gene expression THP-1 macrophages (51)
PE-PGRS33 Induces apoptosis through TLR2 pathway RAW 264.7 and HEK293 cells (52)
Rv0183 Induces inflammation and apoptosis in RAW macrophages Macrophage RAW264.7 cells (53)
Rv0901 Overexpression induces macrophage apoptosis THP-1 macrophages (54)
Rv3499c (Mce4A) Induces apoptosis mediated by TNF-α THP-1 macrophages (55)
PPE37 C-terminal domain induces apoptosis THP-1 macrophages (56)
PE9 (Rv1088)/PE10 (Rv1089) Induces apoptosis by TLR4 pathway THP-1 macrophages (57)
PE_PGRS41 Enhances intracellular survival THP-1 macrophages (58)
PE13/Rv1195 Increases intracellular survival by activating the p38-ERK pathway THP-1 macrophages (59)
PE_PGRS18 Enhances intracellular survival THP-1 macrophages (60)
Apoptosis inhibitors NADH-quinone oxidoreductase subunit G (NuoG) Inhibits apoptosis of infected host cells BALB/c or SCID/Ncr (BALB/c mice) (61)
Protein Phosphatase 2 Phosphatase Activator (PtpA ) Inhibits phagosome acidification and maturation.
Interacts with tripartite motif containing 27 (TRIM27) and suppresses apoptosis
THP-1 macrophages (62)
DUF732 domain-containing protein kinase (Rv3354) Targets the metalloprotease resulting in suppression of apoptosis; destabilizes regulatory cullin-RING ubiquitin E3 enzymatic activity; inhibits constitutive photomorphogenesis 9 (cop9) signaling THP-1 macrophages (63)
MPT64 (Rv1980c) Inhibits apoptosis of macrophages through the NF-kB-miRNA21-Bcl-2 pathway RAW264.7 macrophages (64)
Protein Kinase E (pknE) Mutation increases the expression of genes involved in apoptosis THP-1 macrophages (65)
Rv2456c Inhibits apoptosis through NF-κB and extends the survival of Mtb. Human epithelial cells (A549) & THP-1 macrophages (66)
GroEL2 (Rv0440) Blocks macrophage apoptosis via interaction with mitochondrial mortalin THP-1 and RAW 264.7 cell lines (37)
SecA2 (Rv1821) Controls(?) secretion of a specific subset of proteins and blocks macrophage apoptosis C57BL/6 mice (67)
Oligopeptide transporter subunit (OppD) Transports Mtb and induces apoptosis THP-1 macrophages (68)
Rv3654c/Rv3655c Interacts with AL017 and blocks the extrinsic pathway U937 monocyte-derived macrophage (69)
Necrosis inducers ESAT-6 Results in necrosis of human macrophages mediated by pyrin domain-containing protein-3 (NLRP3) THP-1 macrophages (70)
Channel protein with necrosis-inducing toxin (CpnT /Rv3903c) Induce necrosis of human macrophages through its secreted C-terminal domain known as tuberculosis necrotizing toxin (TNT) RAW 264.7 macrophages (71)
THP-1 macrophages
PE25/PPE41 Recombinant form induces necrosis RAW 264.7 macrophages (72)
Rv2626c High levels of necrosis were observed in THP-1 macrophages infected with MtbH37Rv over-expressing Rv2626c THP-1 macrophages (73)
PPE68 Inactivation decreases necrosis THP-1 macrophages (73)
PPE31 Shortens the life of macrophages infected by Mtb over-expressing PPE31 and promotes mycobacterial survival RAW264.7 macrophages (74)
Pyroptosis inhibitors Rv3364c Binds to the cathepsin G, inhibiting its enzymatic activity and the downstream signal caspase-1. Human monocytic cell line U937-derived macrophages (75)
Inhibits host pyroptosis
Pyroptosis inducers Rv1579c/EST12 Binds to RACK1 to recruit the deubiquitinase UCHL5 leading to NLRP3 inflammasome activation that promotes pyroptosis Human monocytic THP-1 and mouse BMDMs (76)
Zinc metalloprotease 1 (Zmp-1/Rv0198c) Deletion triggers activation of caspase-1/IL-1β inflammasome leading to pyroptosis signaling and improved mycobacterial clearance J774A and RAW 264.7 macrophages (77)
Autophagy inhibitors Enhanced intracellular survival (Eis) Infection with Mtb-Δeis elevates ROS generation and renders the cells highly sensitive to autophagy activation THP-1 macrophages
Mouse BMDM
(78)
ESAT-6 Transient expression of the ESAT-6/CFP-10 fusion inhibits autophagosome formation by decreasing expression levels of ATG genes RAW264.7 macrophages (79)
PtpA Interacts with active-phosphorylated vacuolar protein sorting 33B (VPS33B) and inhibits phagosome-lysosome fusion, impacting autophagy THP-1 (80)
PknG Inhibits phagosome-lysosome fusion, impacting autophagy J774 macrophage cells (81)
ETosis ESAT-6 Induces a high level of intracellular Ca2+ leading to the formation of NETs characterized by extracellular DNA and myeloperoxidase Neutrophils from healthy volunteers (82)

Mycobacterium tuberculosis (Mtb) modulates several types of host cell death upon infection. A list of different Mtb factors and their regulatory role in host cell death are tabulated. TLR2, Toll-like receptor 2; TNFR, tumor necrosis factor-alpha receptor.