RRC ID 19616
Author Miyazato A, Nakamura K, Yamamoto N, Mora-Montes HM, Tanaka M, Abe Y, Tanno D, Inden K, Gang X, Ishii K, Takeda K, Akira S, Saijo S, Iwakura Y, Adachi Y, Ohno N, Mitsutake K, Gow NA, Kaku M, Kawakami K.
Title Toll-like receptor 9-dependent activation of myeloid dendritic cells by Deoxynucleic acids from Candida albicans.
Journal Infect. Immun.
Abstract The innate immune system of humans recognizes the human pathogenic fungus Candida albicans via sugar polymers present in the cell wall, such as mannan and beta-glucan. Here, we examined whether nucleic acids from C. albicans activate dendritic cells. C. albicans DNA induced interleukin-12p40 (IL-12p40) production and CD40 expression by murine bone marrow-derived myeloid dendritic cells (BM-DCs) in a dose-dependent manner. BM-DCs that lacked Toll-like receptor 4 (TLR4), TLR2, and dectin-1, which are pattern recognition receptors for fungal cell wall components, produced IL-12p40 at levels comparable to the levels produced by BM-DCs from wild-type mice, and DNA from a C. albicans pmr1Delta null mutant, which has a gross defect in mannosylation, retained the ability to activate BM-DCs. This stimulatory effect disappeared completely after DNase treatment. In contrast, RNase treatment increased production of the cytokine. A similar reduction in cytokine production was observed when BM-DCs from TLR9(-/-) and MyD88(-/-) mice were used. In a luciferase reporter assay, NF-kappaB activation was detected in TLR9-expressing HEK293T cells stimulated with C. albicans DNA. Confocal microscopic analysis showed similar localization of C. albicans DNA and CpG-oligodeoxynucleotide (CpG-ODN) in BM-DCs. Treatment of C. albicans DNA with methylase did not affect its ability to induce IL-12p40 synthesis, whereas the same treatment completely eliminated the ability of CpG-ODN to induce IL-12p40 synthesis. Finally, impaired clearance of this fungal pathogen was not found in the kidneys of TLR9(-/-) mice. These results suggested that C. albicans DNA activated BM-DCs through a TLR9-mediated signaling pathway using a mechanism independent of the unmethylated CpG motif.
Volume 77(7)
Pages 3056-64
Published 2009-7
DOI 10.1128/IAI.00840-08
PII IAI.00840-08
PMID 19433551
PMC PMC2708591
MeSH Animals CD40 Antigens / biosynthesis Candida albicans / immunology* Candidiasis / immunology Cell Line DNA, Fungal / immunology* Dendritic Cells / immunology* Female Humans Interleukin-12 Subunit p40 / biosynthesis Kidney / microbiology Male Mice Mice, Inbred C57BL Mice, Knockout Myeloid Differentiation Factor 88 / deficiency Myeloid Differentiation Factor 88 / immunology NF-kappa B / biosynthesis Toll-Like Receptor 9 / deficiency Toll-Like Receptor 9 / immunology*
IF 3.256
Times Cited 48
Human and Animal Cells RAW 264 (RCB0535)