Fig 9. A working model—Dectin-2/Dectin-1 and their downstream signals regulate H. capsulatum-induced NLRP3 inflammasome activation.

Dendritic cells being one of the major IL-1β producers in pulmonary H. capsulatum infection, the pathogen is recognized preferentially by Dectin-2 and less so by Dectin-1 in dendritic cells. The recognition triggers Syk-JNK signaling pathway that leads to IL-1β production. Syk-JNK signaling provides signal 1 to induce pro-IL-1β synthesis as well as signal 2 to activate cathepsin B release. While K⁺ efflux also functions as signal 2, it is independent of either receptor. Signal 1 and 2 together promote NLRP3 inflammasome assembly and activation for IL-1β release.