Figure 3.

Signaling crosstalk between myeloid C-type lectins and heterologous receptors. Signaling pathways initiated downstream of C-type lectin receptors (CLRs) interact with surrounding cascades triggered by heterologous receptors. Examples of such crosstalk are illustrated. (A) Dectin-1 coordinates with simultaneous signals from diverse TLRs to modulate the inflammatory response; this interaction can be either positive, as for TLR2/MyD88 (left), or negative, as for TLR9 through a Pyk2/ERK/SOCS-1-dependent pathway (right). (B) In addition, the axis Dectin-1/PI3K/mTOR/Hif-1α generates a switch toward glycolytic metabolism together with an epigenetic footprint, allowing for a “deferred” improved response to TLRs, boosting the inflammatory response. This process is known as trained immunity. (C) A full inflammatory response against Fonsecaea pedrosoi is achieved by synergistic stimulation between Mincle and ligands for TLRs coupled to the MyD88 adaptor (left). However, simultaneous recognition of Fonsecaea monophora by Mincle and Dectin-1 triggers a Mincle-PKB-Mdm2-dependent degradation of Dectin-1-activated IRF1, dampening the expression of protective IL-12p35 (right). (D) DC-SIGN recognition of Fasciola hepatica enhances TLR-induced IL-10 and IL-27p28 (left). Moreover, DC-SIGN sensing of the salivary protein Salp15 from the tick vector Ixodes scapularis dampens inflammatory responses triggered by Borrelia burgdorferi through TLRs (right). Both examples illustrate strategies to escape immune surveillance based on inhibition of T cell proliferation.