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

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-P2X 3 /P2X 2/3 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.