Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages

Abstract

Dectin-1, the major β-glucan receptor in leukocytes, triggers an effective immune response upon fungal recognition. Here we use sortase-mediated transpeptidation, a technique that allows placement of a variety of probes on a polypeptide backbone, to monitor the behavior of labeled functional dectin-1 in live cells with and without fungal challenge. Installation of probes on dectin-1 by sortagging permitted highly specific visualization of functional protein on the cell surface and its subsequent internalization upon ligand presentation. Retrieval of sortagged dectin-1 expressed in macrophages uncovered a unique interaction between dectin-1 and galectin-3 that functions in the proinflammatory response of macrophages to pathogenic fungi. When macrophages expressing dectin-1 are exposed to Candida albicans mutants with increased exposure of β-glucan, the loss of galectin-3 dramatically accentuates the failure to trigger an appropriate TNF-α response.pattern-recognition receptors | sortase A | polysaccharide

The role of pattern recognition receptors in the innate recognition ofCandida albicans

“…108 Interestingly, Galectin-3 also works in association with Dectin-1 on macrophages. 135 When macrophages expressing Dectin-1 are exposed to C. albicans mutants with increased exposure of b-glucan, the loss of Galectin-3 dramatically accentuates the failure to trigger an appropriate TNF-a response. 135 Moreover, the collaboration in immune response may also involve other cell receptors, such as peroxisome proliferator-activated receptor (PPAR)-g and CD44.…”

“…135 When macrophages expressing Dectin-1 are exposed to C. albicans mutants with increased exposure of b-glucan, the loss of Galectin-3 dramatically accentuates the failure to trigger an appropriate TNF-a response. 135 Moreover, the collaboration in immune response may also involve other cell receptors, such as peroxisome proliferator-activated receptor (PPAR)-g and CD44. PPAR-g is expressed in various immune cells and acts as a transcriptional repressor to inhibit the transcription of many proinflammatory cytokines.…”

Dendritic cell interactions withHistoplasmaandParacoccidioides

“…Gal-3 has been shown to interact with dectin-1 and TLR-2. 77,78 Previous studies using knockout mice have demonstrated that TGF-b1 and IL-6 fuel Th17 differentiation, while IL-23 facilitates the differentiation and sustains the Th17 cells. [79][80][81] IL-17A acts on a variety of cell types to promote inflammation 82 and helps eradicate extracellular pathogens.…”

The Cek1‑mediated MAP kinase pathway regulates exposure of α‑1,2 and β‑1,2‑mannosides in the cell wall ofCandida albicansmodulating immune recognition

“…6,7 This immune receptor has been shown to associate with dectin-1, that specifically recognizes fungal b-1,3-glucan, to mediate fungal uptake, although galectin-3 is not essential for this process, working together in the proinflammatory response of macrophages. 18 Interestingly, dectin-1 mediates the increased binding and phagocytosis of cek1 mutants due to its enhanced cell wall glucan exposure, and the activation of intracellular signaling pathways of human dendritic cells and macrophages. 43 The observation of galectin-3 surrounding cek1 yeast cells during their interaction with macrophages, especially at early time points, suggest a role for both dectin-1 and galectin-3 in the increased recognition and phagocytosis of this mutant.…”