Figure 2.

Complex signaling pathways downstream Dectin-1 leading to ROS production. The generation of ROS after Dectin-1 engagement is a relevant event. Different signaling pathways are involved in this process leading to the activation of the NADPH oxidase as a central hub. The uptake of large particulate Dectin-1 ligands triggers a Syk-independent, PI3K-dependent pathway. An alternative Syk/SHP-2/ERK pathway can be also triggered, which can be regulated by the SHIP-1 phosphatase. IFN-IIIs are produced in vivo in response to Aspergillus fumigatus in a Dectin-1-dependent manner, although their cellular source has not been addressed (represented by dotted lines). These IFN-IIIs are recognized by their specific receptor (IFN-λR), triggering a not fully described STAT1-mediated pathway, that ends up with ROS production. The mitochondrial metabolism also contributes to generate ROS in response to Dectin-1 ligands. In addition to the well-described microbicidal role of ROS, they can act as second messenger signals, exemplified in this figure by the activation of the inflammasome, leading to the processing of pro-IL-1β into bioactive IL-1β.