Fig 1.
Activation of inflammasomes by fungal pathogens.
Four inflammasome complexes are activated when engaged by systemic fungal pathogens. Candida, Aspergillus, Cryptococcus, and Paracoccidioides trigger priming-associated receptors (e.g., dectin-1 and TLR2), thereby promoting the first step (priming) of inflammasome activation. All four pathogens activate the canonical caspase-1-dependent NLRP3 inflammasome by inducing ROS, K+ efflux, and cathepsin B release. Candida-secreted aspartic proteases (Saps) are internalized and also activate the NLRP3 inflammasome via induction of K+ efflux and ROS production. Aspergillus activates both caspase-1- and caspase-8-dependent inflammasomes, requiring the simultaneous activation of the NLRP3 and AIM2 receptors. In terms of NLRP3-independent inflammasomes, Candida and Aspergillus activate a caspase-8-dependent inflammasome that requires the engagement of dectin-1, Syk signaling, and ASC recruitment. In addition, Candida triggers the NLRC4 inflammasome.