Abstract
SummaryCandida 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.
Highlights
Candida albicans is an opportunistic fungus that thrives in the skin, mouth, vagina, and nipples
C. albicansderived b-glucan has the ability to enhance histamine-independent pruritus, and vesicular nucleotide transporter (VNUT) inhibitor clodronate can be used to treat unpleasant feelings induced by b-glucan
We focused on components of the fungal body and found that b-glucan was secreted from the fungus when cultured for 2 hr at 37C (Figure 1B). b-Glucan is released as C. albicans-derived soluble b-glucan (CSBG) or C. albicans-derived particulate b-glucan (CPBG) in the infected regions (Figure S1F)
Summary
Candida albicans is an opportunistic fungus that thrives in the skin, mouth, vagina, and nipples. Immunodeficiency within hosts and poorly controlled diabetes have increased the rates of invasive C. albicans infections, evoking skin or oral pain. It has been well established that ion channels expressed in primary sensory neurons play a critical role in the sensing of pain (Woolf and Costigan, 1999). A recent report suggested that nociceptors directly sense Gram-positive bacterial components such as a-hemolysin (Chiu et al, 2013). Another group reported that Gram-negative bacterial components, such as lipopolysaccharide, are sensed by TRPA1 (Meseguer et al, 2014). Nociceptors may directly sense bacterial infection like innate immune cells
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