Caspase-1 Activation via Rho GTPases: A Common Theme in Mucosal Infections?

Caspase-1 is an important converging point for danger signals initiating inflammation and defense. Recent work suggests that RhoGTPase activation and/or cytoskeletal disturbance may represent a novel pathway eliciting caspase-1 responses that are subverted by several enteropathogenic bacteria. The enteropathogen Salmonella Typhimurium employs the type III effector protein SopE, an activator (guanine nucleotide exchange factor [GEF]) for RhoGTPases, to elicit caspase-1 maturation and release of the pro-inflammatory cytokine IL-1b to trigger gut inflammation in vivo. Recently, a whole new family of pathogenencoded RhoGTPase GEFs has been discovered, including Map, IpgB1, and IpgB2 from enteropathogenic Escherichia coli and Shigella spp.. We will discuss the evidence suggesting that these virulence factors may also activate caspase-1 signaling.