Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors

Abstract

The fungal pathogen Candida albicans has a multilayered cell wall composed of an outer layer of proteins glycosylated with N-or O-linked mannosyl residues and an inner skeletal layer of β-glucans and chitin. We demonstrate that cytokine production by human mononuclear cells or murine macrophages was markedly reduced when stimulated by C. albicans mutants defective in mannosylation. Recognition of mannosyl residues was mediated by mannose receptor binding to N-linked mannosyl residues and by TLR4 binding to O-linked mannosyl residues. Residual cytokine production was mediated by recognition of β-glucan by the dectin-1/ TLR2 receptor complex. C. albicans mutants with a cell wall defective in mannosyl residues were less virulent in experimental disseminated candidiasis and elicited reduced cytokine production in vivo. We concluded that recognition of C. albicans by monocytes/macrophages is mediated by 3 recognition systems of differing importance, each of which senses specific layers of the C. albicans cell wall.

Synergistic regulation of Pseudomonas aeruginosa‐induced cytokine production in human monocytes by mannose receptor and TLR2

“…MR synergizes with TLR and lectins in immune sensing of C. albicans [45] and regulates proinflammatory cytokine production induced by Mycobacteria through interfering with TLR2-mediated signaling [46]. MR-mediated signaling could be positive [47] or negative [48,49] depending on the structure of stimulus or the site of infection.…”

Transcriptional and inflammasome‐mediated pathways for the induction of IL‐1β production by Mycobacterium tuberculosis

“…-1922 Innate immunity Isolation of PBMC and stimulation of cytokine production After informed consent, venous blood was drawn from the cubital vein of patients and healthy volunteers into three 10-mL EDTA tubes (Monoject, s-Hertogenbosch, Netherlands). Isolation of PBMC was performed as described elsewhere [48], with minor modifications. The PBMC fraction was obtained by density centrifugation of blood diluted 1:1 in pyrogen-free saline over Ficoll-Paque (Pharmacia Biotech, Uppsala, Sweden).…”

“…Isolation of PBMC was performed as described elsewhere [48], with minor modifications. The PBMC fraction was obtained by density centrifugation of blood diluted 1:1 in pyrogen-free saline over Ficoll-Paque (Pharmacia Biotech, Uppsala, Sweden).…”

CD8– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

“…In addition, SIGNR1 [29] and the mannose-receptor (MR) can also bind fungal components, but these receptors are mainly expressed by macrophages [11,30,31].…”

“…Of these receptors, TLR2 and the DCassociated C-type lectin (dectin-1) are specifically involved in recognition of fungal components [7][8][9]. Zymosan and fungal pathogens like C. albicans and A. fumigatus are sensed by TLR2 that signals via myeloid differentiation factor 88 (MyD88), resulting in NF-jB activation and the production of cytokines [10][11][12][13]. The importance of this signaling cascade can be inferred from the fact that MyD88-knockout mice show an increased susceptibility to fungal infections [14,15].…”