Murine caspase-11, and its human homologs caspase-4 and caspase-5, are mammalian intracellular receptor proteases activated by TLR4 and TLR3 signaling during the innate immune response.
Caspase-11, also termed the non-canonical inflammasome, is activated by TLR3/TLR4-TRIF signaling and directly binds cytosolic lipopolysaccharide (LPS), a major structural element of Gram-negative bacterial cell walls.
LPS binding to TLR4 subsequently causes initiation of the MyD88 and TRIF signaling pathways, leading to expression of pro-inflammatory molecules and cytokines.
However, in 2013 it was shown that TLR4 knockout mice treated with the TLR3 ligand poly I:C still die of toxic shock induced by LPS treatment.
Conversely, it was also found that poly I:C treated TLR4 and caspase-11 double knockout mice do not develop toxic shock in response to LPS.
[1] Caspase-11 activation results in pyroptosis, a form of lytic cell death that releases inflammatory molecules such as ATP, HMGB1 and IL-1α from the cytosol.
Caspase-11 has been shown to be activated by Burkholderia pseudomallei, Gram-negative bacteria found in the soil of southeast Asia that cause severe melioidosis.