The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception

Kenta Maruyama, Yasunori Takayama, Erika Sugisawa, Yu Yamanoi, Takashi Yokawa, Takeshi Kondo, Ken-ichi Ishibashi, Bikash Ranjan Sahoo, Naoki Takemura, Yuki Mori, Hisashi Kanemaru, Yutaro Kumagai, Mikaël M. Martino, Yoshichika Yoshioka, Hisao Nishijo, Hiroki Tanaka, Atsushi Sasaki, Naohito Ohno, Yoichiro Iwakura, Yoshinori Moriyama & 3 others Masatoshi Nomura, Shizuo Akira, Makoto Tominaga

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Summary Candida albicans infection can cause skin, vulvar, or oral pain. Despite the obvious algesic activity of C. albicans, the molecular mechanisms of fungal nociception remain largely unknown. Here we show that the C. albicans-specific signaling pathway led to severe mechanical allodynia. We discovered that C. albicans-derived β-glucan stimulated nociceptors depending on Dectin-1, and two pathways in inflammatory pain. The major pathway operates via the Dectin-1-mediated ATP-P2X3/P2X2/3 axis through intercellular relationships between keratinocytes and primary sensory neurons, which depends on the ATP transporter vesicular nucleotide transporter (VNUT). The other pathway operates via the Dectin-1-mediated PLC-TRPV1/TRPA1 axis in primary sensory neurons. Intriguingly, C. albicans-derived β-glucan has the ability to enhance histamine-independent pruritus, and VNUT inhibitor clodronate can be used to treat unpleasant feelings induced by β-glucan. Collectively, this is the first report to indicate that Dectin-1 and VNUT mediated innate sensory mechanisms that detect fungal infection.
Original languageEnglish
Pages (from-to)306-318
Number of pages13
JournaliScience
Volume6
DOIs
Publication statusPublished - 31 Aug 2018

Keywords

  • Molecular Mechanism of Behavior, Molecular Neuroscience, Medical Microbiology

Cite this

Maruyama, K., Takayama, Y., Sugisawa, E., Yamanoi, Y., Yokawa, T., Kondo, T., ... Tominaga, M. (2018). The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception. iScience, 6, 306-318. https://doi.org/10.1016/j.isci.2018.08.007
Maruyama, Kenta ; Takayama, Yasunori ; Sugisawa, Erika ; Yamanoi, Yu ; Yokawa, Takashi ; Kondo, Takeshi ; Ishibashi, Ken-ichi ; Sahoo, Bikash Ranjan ; Takemura, Naoki ; Mori, Yuki ; Kanemaru, Hisashi ; Kumagai, Yutaro ; Martino, Mikaël M. ; Yoshioka, Yoshichika ; Nishijo, Hisao ; Tanaka, Hiroki ; Sasaki, Atsushi ; Ohno, Naohito ; Iwakura, Yoichiro ; Moriyama, Yoshinori ; Nomura, Masatoshi ; Akira, Shizuo ; Tominaga, Makoto. / The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception. In: iScience. 2018 ; Vol. 6. pp. 306-318.
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abstract = "Summary Candida albicans infection can cause skin, vulvar, or oral pain. Despite the obvious algesic activity of C. albicans, the molecular mechanisms of fungal nociception remain largely unknown. Here we show that the C. albicans-specific signaling pathway led to severe mechanical allodynia. We discovered that C. albicans-derived β-glucan stimulated nociceptors depending on Dectin-1, and two pathways in inflammatory pain. The major pathway operates via the Dectin-1-mediated ATP-P2X3/P2X2/3 axis through intercellular relationships between keratinocytes and primary sensory neurons, which depends on the ATP transporter vesicular nucleotide transporter (VNUT). The other pathway operates via the Dectin-1-mediated PLC-TRPV1/TRPA1 axis in primary sensory neurons. Intriguingly, C. albicans-derived β-glucan has the ability to enhance histamine-independent pruritus, and VNUT inhibitor clodronate can be used to treat unpleasant feelings induced by β-glucan. Collectively, this is the first report to indicate that Dectin-1 and VNUT mediated innate sensory mechanisms that detect fungal infection.",
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author = "Kenta Maruyama and Yasunori Takayama and Erika Sugisawa and Yu Yamanoi and Takashi Yokawa and Takeshi Kondo and Ken-ichi Ishibashi and Sahoo, {Bikash Ranjan} and Naoki Takemura and Yuki Mori and Hisashi Kanemaru and Yutaro Kumagai and Martino, {Mika{\"e}l M.} and Yoshichika Yoshioka and Hisao Nishijo and Hiroki Tanaka and Atsushi Sasaki and Naohito Ohno and Yoichiro Iwakura and Yoshinori Moriyama and Masatoshi Nomura and Shizuo Akira and Makoto Tominaga",
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Maruyama, K, Takayama, Y, Sugisawa, E, Yamanoi, Y, Yokawa, T, Kondo, T, Ishibashi, K, Sahoo, BR, Takemura, N, Mori, Y, Kanemaru, H, Kumagai, Y, Martino, MM, Yoshioka, Y, Nishijo, H, Tanaka, H, Sasaki, A, Ohno, N, Iwakura, Y, Moriyama, Y, Nomura, M, Akira, S & Tominaga, M 2018, 'The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception' iScience, vol. 6, pp. 306-318. https://doi.org/10.1016/j.isci.2018.08.007

The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception. / Maruyama, Kenta; Takayama, Yasunori; Sugisawa, Erika; Yamanoi, Yu; Yokawa, Takashi; Kondo, Takeshi; Ishibashi, Ken-ichi; Sahoo, Bikash Ranjan; Takemura, Naoki; Mori, Yuki; Kanemaru, Hisashi; Kumagai, Yutaro; Martino, Mikaël M.; Yoshioka, Yoshichika; Nishijo, Hisao; Tanaka, Hiroki; Sasaki, Atsushi; Ohno, Naohito; Iwakura, Yoichiro; Moriyama, Yoshinori; Nomura, Masatoshi; Akira, Shizuo; Tominaga, Makoto.

In: iScience, Vol. 6, 31.08.2018, p. 306-318.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception

AU - Maruyama, Kenta

AU - Takayama, Yasunori

AU - Sugisawa, Erika

AU - Yamanoi, Yu

AU - Yokawa, Takashi

AU - Kondo, Takeshi

AU - Ishibashi, Ken-ichi

AU - Sahoo, Bikash Ranjan

AU - Takemura, Naoki

AU - Mori, Yuki

AU - Kanemaru, Hisashi

AU - Kumagai, Yutaro

AU - Martino, Mikaël M.

AU - Yoshioka, Yoshichika

AU - Nishijo, Hisao

AU - Tanaka, Hiroki

AU - Sasaki, Atsushi

AU - Ohno, Naohito

AU - Iwakura, Yoichiro

AU - Moriyama, Yoshinori

AU - Nomura, Masatoshi

AU - Akira, Shizuo

AU - Tominaga, Makoto

PY - 2018/8/31

Y1 - 2018/8/31

N2 - Summary Candida albicans infection can cause skin, vulvar, or oral pain. Despite the obvious algesic activity of C. albicans, the molecular mechanisms of fungal nociception remain largely unknown. Here we show that the C. albicans-specific signaling pathway led to severe mechanical allodynia. We discovered that C. albicans-derived β-glucan stimulated nociceptors depending on Dectin-1, and two pathways in inflammatory pain. The major pathway operates via the Dectin-1-mediated ATP-P2X3/P2X2/3 axis through intercellular relationships between keratinocytes and primary sensory neurons, which depends on the ATP transporter vesicular nucleotide transporter (VNUT). The other pathway operates via the Dectin-1-mediated PLC-TRPV1/TRPA1 axis in primary sensory neurons. Intriguingly, C. albicans-derived β-glucan has the ability to enhance histamine-independent pruritus, and VNUT inhibitor clodronate can be used to treat unpleasant feelings induced by β-glucan. Collectively, this is the first report to indicate that Dectin-1 and VNUT mediated innate sensory mechanisms that detect fungal infection.

AB - Summary Candida albicans infection can cause skin, vulvar, or oral pain. Despite the obvious algesic activity of C. albicans, the molecular mechanisms of fungal nociception remain largely unknown. Here we show that the C. albicans-specific signaling pathway led to severe mechanical allodynia. We discovered that C. albicans-derived β-glucan stimulated nociceptors depending on Dectin-1, and two pathways in inflammatory pain. The major pathway operates via the Dectin-1-mediated ATP-P2X3/P2X2/3 axis through intercellular relationships between keratinocytes and primary sensory neurons, which depends on the ATP transporter vesicular nucleotide transporter (VNUT). The other pathway operates via the Dectin-1-mediated PLC-TRPV1/TRPA1 axis in primary sensory neurons. Intriguingly, C. albicans-derived β-glucan has the ability to enhance histamine-independent pruritus, and VNUT inhibitor clodronate can be used to treat unpleasant feelings induced by β-glucan. Collectively, this is the first report to indicate that Dectin-1 and VNUT mediated innate sensory mechanisms that detect fungal infection.

KW - Molecular Mechanism of Behavior, Molecular Neuroscience, Medical Microbiology

U2 - 10.1016/j.isci.2018.08.007

DO - 10.1016/j.isci.2018.08.007

M3 - Article

VL - 6

SP - 306

EP - 318

JO - iScience

JF - iScience

SN - 2589-0042

ER -

Maruyama K, Takayama Y, Sugisawa E, Yamanoi Y, Yokawa T, Kondo T et al. The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception. iScience. 2018 Aug 31;6:306-318. https://doi.org/10.1016/j.isci.2018.08.007