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

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...

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Published in:iScience 2018-08, Vol.6, p.306-318
Main Authors: 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
Format: Article
Language:English
Subjects:
Medical Microbiology
Molecular Mechanism of Behavior
Molecular Neuroscience
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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. [Display omitted] •β-Glucan-induced pain is abolished in Dectin-1- and TRPV1/TRPA1-deficient mice•β-–Glucan stimulates nociceptors via Dectin-1-PLC axis, activating neurons•β-Glucan-induced allodynia is dependent on extracellular ATP and VNUT•VNUT inhibitor clodronate can be used to treat β-glucan-induced allodynia Molecular Mechanism of Behavior; Molecular Neuroscience; Medical Microbiology
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2018.08.007