Figure 1.
Caspase-11 effector functions and models for caspase-11 activation.
(A) Caspase-11 effector functions. Active caspase-11 cooperates with components of the NLRP3 inflammasome to induce caspase-1-dependent maturation of pro-IL-1β and pro-IL-18. It remains to be determined if caspase-11 activates NLRP3 directly or if additional signals are required. Active caspase-11 also induces cell lysis, resulting in the release of danger signals such as IL-1α and HMGB-1. Finally, during L. pneumophila infections, caspase-11 controls phagosome-lysosome fusion through the phosphorylation state of cofilin. (B, C) Two distinct models for caspase-11 activation. (B) Receptor/scaffold-mediated activation. Detection of Gram-negative bacteria by TLR4 results in the activation of NFκB and subsequent expression of pro-IL-1β and pro-caspase-11. Signaling through Trif and IRF3 induces expression of type-I-IFNs. Type-I-IFN signaling through IFNαR contributes to pro-caspase-11 expression and induces the expression of an uncharacterized receptor/activator of caspase-11. Activation of caspase-11 by this factor might require an additional undefined signal, stemming from the bacterial infection. (C) Autoactivation of pro-caspase-11. Detection of Gram-negative bacteria by TLR4 results in the activation of NFκB and subsequent expression of pro-IL-1β. Signaling through Trif and IRF3 induces expression of type-I-IFNs, which induces pro-caspase-11 expression. Pro-caspase-11 autoactivates, presumably once a concentration threshold is reached.