Toll-like receptor 9-dependent activation of myeloid dendritic cells by deoxynucleic acids from Candida albicans

Akiko Miyazato, Kiwamu Nakamura, Natsuo Yamamoto, Hector M Mora-Montes, Misuzu Tanaka, Yuzuru Abe, Daiki Tanno, Ken Inden, Xiao Gang, Keiko Ishii, Kiyoshi Takeda, Shizuo Akira, Shinobu Saijo, Yoichiro Iwakura, Yoshiyuki Adachi, Naohito Ohno, Kotaro Mitsutake, Neil A R Gow, Mitsuo Kaku, Kazuyoshi Kawakami

Research output: Contribution to journalArticle

66 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)3056-3064
Number of pages9
JournalInfection and Immunity
Volume77
Issue number7
Early online date11 May 2009
DOIs
Publication statusPublished - Jul 2009

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Toll-Like Receptor 9
Myeloid Cells
Candida albicans
Dendritic Cells
Acids
Interleukins
Bone Marrow
DNA
Oligodeoxyribonucleotides
Cell Wall
Cytokines
Pattern Recognition Receptors
Mannans
beta-Glucans
Toll-Like Receptor 4
Deoxyribonucleases
NF-kappa B
Cellular Structures
Ribonucleases
Luciferases

Keywords

  • animals
  • antigens, CD40
  • Candida albicans
  • candidiasis
  • cell line
  • DNA, fungal
  • dendritic cells
  • female
  • humans
  • interleukin-12 subunit p40
  • kidney
  • male
  • mice
  • mice, inbred C57BL
  • mice, knockout
  • myeloid differentiation factor 88
  • NF-kappa B
  • toll-like receptor 9

Cite this

Miyazato, A., Nakamura, K., Yamamoto, N., Mora-Montes, H. M., Tanaka, M., Abe, Y., ... Kawakami, K. (2009). Toll-like receptor 9-dependent activation of myeloid dendritic cells by deoxynucleic acids from Candida albicans. Infection and Immunity, 77(7), 3056-3064. https://doi.org/10.1128/IAI.00840-08

Toll-like receptor 9-dependent activation of myeloid dendritic cells by deoxynucleic acids from Candida albicans. / Miyazato, Akiko; Nakamura, Kiwamu; Yamamoto, Natsuo; Mora-Montes, Hector M; Tanaka, Misuzu; Abe, Yuzuru; Tanno, Daiki; Inden, Ken; Gang, Xiao; Ishii, Keiko; Takeda, Kiyoshi; Akira, Shizuo; Saijo, Shinobu; Iwakura, Yoichiro; Adachi, Yoshiyuki; Ohno, Naohito; Mitsutake, Kotaro; Gow, Neil A R; Kaku, Mitsuo; Kawakami, Kazuyoshi.

In: Infection and Immunity, Vol. 77, No. 7, 07.2009, p. 3056-3064.

Research output: Contribution to journalArticle

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, NAR, Kaku, M & Kawakami, K 2009, 'Toll-like receptor 9-dependent activation of myeloid dendritic cells by deoxynucleic acids from Candida albicans', Infection and Immunity, vol. 77, no. 7, pp. 3056-3064. https://doi.org/10.1128/IAI.00840-08
Miyazato, Akiko ; Nakamura, Kiwamu ; Yamamoto, Natsuo ; Mora-Montes, Hector M ; Tanaka, Misuzu ; Abe, Yuzuru ; Tanno, Daiki ; Inden, Ken ; Gang, Xiao ; Ishii, Keiko ; Takeda, Kiyoshi ; Akira, Shizuo ; Saijo, Shinobu ; Iwakura, Yoichiro ; Adachi, Yoshiyuki ; Ohno, Naohito ; Mitsutake, Kotaro ; Gow, Neil A R ; Kaku, Mitsuo ; Kawakami, Kazuyoshi. / Toll-like receptor 9-dependent activation of myeloid dendritic cells by deoxynucleic acids from Candida albicans. In: Infection and Immunity. 2009 ; Vol. 77, No. 7. pp. 3056-3064.
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AU - Inden, Ken

AU - Gang, Xiao

AU - Ishii, Keiko

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AU - Saijo, Shinobu

AU - Iwakura, Yoichiro

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KW - kidney

KW - male

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KW - mice, inbred C57BL

KW - mice, knockout

KW - myeloid differentiation factor 88

KW - NF-kappa B

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