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
N1 - Funding Information:
We thank Dr. B. Hube for providing the Ece1-knockout C . albicans (Ece1Δ/Δ, strain M2057); Dr. H. J. Fehling for providing Rosa26-tdRFP reporter mice; C. Okahata, K. Shinno, and H. Omori for technical assistance; Dr. S. Saijo, Dr. O. Takeuchi, and K. Asakawa for valuable discussions; and E. Kamada for secretarial assistance. We also thank Dr. D. Julius (University of California San Francisco) for providing the TRPV1 and TRPA1 knockout mice. This research was supported by a grant from the Osaka University MEET project (to K.M.), the Takeda Science Foundation (K.M.), a KAKENHI Grant-in-Aid for Challenging Exploratory Research ( JP26670663 and JP16K15665 to K.M.), a Translational Research Network Program from Japan Agency for Medical Research and Development AMED (K.M.), a KAKENHI Grant-in-Aid for Young Scientists A ( JP15H05686 to K.M.), a KAKENHI Grant-in-Aid for Research Grant B ( 18H02970 to K.M.), the Japan Intractable Diseases Research Foundation (K.M.), the Senri Life Science Foundation Kishimoto grant (K.M.), the Japan Prize Foundation (K.M.), the Mochida Memorial Foundation (K.M.), the National Institute for Physiological Science (General Collaborative Project to K.M. and M.T.), the Osaka University International Joint Research Promotion Program (S.A.), the Japan Rheumatism Foundation (K.M.), the Akashi Medical Research Foundation (K.M.), the Kanzawa Medical Research Foundation (K.M.), the Terumo Foundation for Life Sciences and Arts (K.M.), and the Life Science Foundation (K.M.).
Publisher Copyright:
© 2018 The Author(s)
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
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 - Medical Microbiology
KW - Molecular Mechanism of Behavior
KW - Molecular Neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85063043392&partnerID=8YFLogxK
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 -