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

Abstract

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.

• Authors: 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, Masatoshi Nomura, Shizuo Akira, Makoto Tominaga
• Journal: iScience (iScience) Vol. 6 Pg. 306-318 (Aug 31 2018) ISSN: 2589-0042 [Electronic] United States
• PMID: 30240621 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.