Figure 4.

Schematic of immune signaling cascades triggered by Cryptococcus neoformans recognition. (a) Dectin-1 signaling pathway. Dectin-1 can induce both Syk-dependent and Raf (Syk-independent) pathways. Dectin-1 can activate macrophages through the Syk pathway, triggering phagocytosis; following phagocytosis, Dectin-1 activation, coupled to ROS production, contributes to inflammasome activation or fungal killing and activates the transcription factor NF-κB through CARD9, triggering inflammatory cytokine production. The Raf-1 (Syk-independent) pathway enhances NF-κB and inflammatory cytokines. (b) Inflammasome pathway. The Syk-dependent pathway requires combination of two signals. The first signal, which can be mediated by TLR activation, together with a second signal, such as ROS production and/or lysosomal damage, induces the oligomerization of the NLRP3 complex, activation of caspase 1, and production of IL-1β. Abbreviations: ASC, apoptosis-associated speck-like protein containing a C-terminal CARD; Bcl10, B cell leukemia/lymphoma 10; CARD9, caspase recruitment domain–containing protein 9; CLR, C-type lectin receptor; IL, interleukin; MALT-1, mucosa-associated lymphoid tissue 1; NF-κB, nuclear factor κ-light-chain enhancer of activated B cells; NLRP3, Nod-like receptor family, pyrin domain–containing 3; PLCγ2, phospholipase Cγ2; ROS, reactive oxygen species; Syk, spleen tyrosine kinase; TLR, Toll-like receptor; TNF-α, tumor necrosis factor α