Inflammasomes, Autophagy, and Cell Death: The Trinity of Innate Host Defense against Intracellular Bacteria

Table 1

Interplay of Burkholderia pseudomallei (Bp), Mycobacterium tuberculosis (Mtb), and Legionella pneumophila (Lp) with autophagy, inflammasomes, and host cell death modes.

	Autophagy	Inflammasomes	Cell death
Bp	T3SS effectors aid bacterial escape to the cytosol [13, 14].; Bacteria evade autophagy [27].	LPS is a weak agonist of TLR4 [54].; Cytosolic LPS activates caspase 11 [85].; Flagellin activates TLR5 [63] and NAIP5/NLRC4 [90, 114].	Caspase 1 and caspase 11 mediate pyroptosis [85, 112, 113].; Caspase 1- and caspase 11-knockout mice are highly susceptible to pyroptosis [85, 113].; T3SS BsaK induces pyroptosis [114].
Mtb	Autophagy restricts Mtb growth [30].; SapM prevents phagosome maturation [17].; Viable Mtb disrupts phagolysosome maturation [31].	ESX-1 induces lysosomal release of IL1β and IL18 [95].; ESAT-6 activates NLRP3 and ruptures phagosomes [94].; Mtb DNA released by ESX-1 activates cGAS/STING/IFNI [96, 99].	Virulent Mtb promotes macrophage necrosis via ESX-1 [95, 109].; Phagosome rupture induces necrosis [97].; Virulent Mtb induces IFNI to suppress inflammasomes [41] and promotes necrosis [97].
Lp	RavZ inhibits autophagy [32].; T4SS Icm/Dot promotes specialized vacuoles for bacterial replication [16, 23].	Lipopeptides activate TLR2 and limit bacterial replication [57, 58].; Flagellin activates NAIP5/NLRC4 [73] and enhances autophagy [92].; cGAS/STING/IFNI activation targets vacuoles to eliminate bacteria [118].	NAIP5/NLRC4 activation promotes pyroptosis [73].; Coordination of pyroptosis and autophagy by inflammasomes prevents excessive cell death in C57/B6 mice [92].