Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14- and Toll-like receptor 4-dependent manner.
The cytokine-inducing activities of fungal polysaccharides were examined in human monocytes in culture, with special reference to CD14 and Toll-like receptors (TLRs). Tumor necrosis factor alpha (TNF-alpha) production by monocytes was markedly induced in a dose-dependent manner upon stimulation with cell walls from Candida albicans and mannan from Saccharomyces cerevisiae and C. albicans, although relatively high concentrations (10 to 100 microg/ml) of stimulants were required for activation as compared with the reference lipopolysaccharide (LPS) (1 to 10 ng/ml). The yeast form C. albicans and its mannan and cell wall fractions exhibited higher TNF-alpha production than respective preparations from the hyphal form. Only slight TNF-alpha production was induced by the S. cerevisiae glucan. The TNF-alpha production triggered by reference LPS and purified fungal mannans required the presence of LPS-binding protein (LBP), and these responses were inhibited by anti-CD14 and anti-TLR4 antibodies, but not by anti-TLR2 antibody. In contrast to the activity of LPS, the activity of purified S. cerevisiae mannan was not inhibited by polymyxin B. These findings suggested that the mannan-LBP complex is recognized by CD14 on monocytes and that signaling through TLR4 leads to the production of proinflammatory cytokines in a manner similar to that induced by LPS.
Tada
Hiroyuki
H
Nemoto
Eiji
E
Shimauchi
Hidetoshi
H
Watanabe
Toshihiko
T
Mikami
Takeshi
T
Matsumoto
Tatsuji
T
Ohno
Naohito
N
Tamura
Hiroshi
H
Shibata
Ken-ichiro
K
Akashi
Sachiko
S
Miyake
Kensuke
K
Sugawara
Shunji
S
Takada
Haruhiko
H
D000209:Acute-Phase Proteins; D002176:Candida albicans / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D004731:Endotoxins / Q000032:analysis; D005936:Glucans / Q000032:analysis; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000737:chemistry / Q000502:physiology*; D008351:Mannans / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D011112:Polymyxin B / Q000378:metabolism; D011134:Polysaccharides / Q000819:agonists / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015003:Yeasts / Q000378:metabolism; D015054:Zymosan / Q000032:analysis; D047071:beta-Glucans; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D004731:Endotoxins; D005936:Glucans; D018950:Lipopolysaccharide Receptors; D008351:Mannans; D008562:Membrane Glycoproteins; D011112:Polymyxin B; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D047071:beta-Glucans; D000099231:Lipopolysaccharide-Binding Protein; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C033363:beta-1,3-glucan