Fig. 1.

Purinergic receptor stimulation and inflammasome activation alter chlamydial development. Prolonged adenosine exposure suppresses chlamydial development via stimulation of host Gs protein- and adenylyl cyclase-coupled A2b receptors, and ADP or ATP mediated activation of P2X4 and P2X7 receptors also leads to reduced chlamydial growth or P2X7 mediated chlamydial killing, depending on the concentration of purine nucleotides and host cell type. Assembly of pro-caspase-1, NLR-family member sensor proteins, and ASC adaptor proteins into multimeric inflammasomes is required to generate active caspase-1, and follows combinatorial signaling events activating multiple upstream pathways, which may include ATP stimulation of P2X7 receptors, or other DAMP-dependent signaling pathways. Inflammatory triggers such as lipopolysaccharide (LPS) activation of TLR4 leads to production of pro-IL-1β, but inflammasome mediated production of active caspase-1 is required for generation of secreted pro-inflammatory IL-1β. Inflammasome activation mediated cleavage of pro-caspase-1, yielding active caspase-1, also contributes directly to growth of intracellular chlamydiae.