The principal cell surface pattern recognition receptors involved in <i>Candida</i> recognition.

<p>The Toll-like receptor 2 (TLR2) and TLR4 recognize phospholipomannans and <i>O</i>-linked mannans, respectively, whereas TLR9 within the cytosol recognizes fungal DNA, and intracellular TLR7 (not depicted) recognizes fungal RNA. TLR2 forms heterodimers with TLR1 or TLR6 for downstream signaling (not depicted), whereas TLR4 forms homodimers. Galectin-3, together with TLR2, recognizes β-mannosides. The membrane-bound C-type lectins dendritic cell–specific ICAM3-grabbing non-integrin (DC-SIGN), macrophage-inducible C-type lectin (Mincle), and macrophage mannose receptor (MR) recognize mannose-rich <i>Candida</i> structures. In addition, dectin-1 recognizes β-glucans, and dectin 2, together with the Fcγ receptor (FcγR), recognizes mannans. The complement receptor 3 (CR3) on neutrophils also recognizes β-glucans. Moreover, the NOD-like receptor NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) forms an inflammasome complex with ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) and caspase 1, which leads to interleukin-1β (IL-1β) production. In addition, downstream dectin-1 signaling through caspase recruitment domain-containing protein 9 (CARD9) leads to non-canonical inflammasome activation and IL-1β production via caspase 8. IFNs, interferons; NF-κB, nuclear factor-κB; Syk, spleen tyrosine kinase; IRF3, interferon regulatory factor 3; TRIF, TIR-domain-containing adapter-inducing interferon-β; MyD88, myeloid differentiation primary response gene 88; BCL-10, B-cell lymphoma/leukemia 10; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; TRAF6, TNF receptor–associated factor 6; IRAK, interleukin-1 receptor-associated kinase.