Figure 4.

CLRs mediate inflammasome activation. Fungi can activate the NLRP3 and NLRC4 inflammasomes, inducing the caspase-1-mediated cleavage of pro-IL-1β and production of bioactive IL-1β. While CLR, such as Dectin-1, can drive the induction of pro-IL-1β, it is unclear how the intracellularly-located NLR actually sense fungi. Activation of these receptors may directly involve CLR, as this process was found to require Syk kinase (as well as fungal uptake, the respiratory burst and potassium efflux). More recently, Dectin-1 has been shown to be able to activate the noncanonical caspase-8 inflammasome, which interacts directly with the Card9-Bcl-10-MALT1 complex. Activation of caspase-8 by recruitment to this signaling complex results in the cleavage of pro-IL-1β. Assembly of these inflammasomes also involves other components, including ASC (not shown).