Fig 3.

Fungal and Viral PAMPs that cause nociception. Candida albicans, an opportunistic fungal pathogen that causes painful candidiasis, can be sensed by nociceptors through their cell wall components, including Zymosan and β-glucan. Zymosans and β-glucan can be sensed by PRRs including Dectin-1 and TLR2 to activate nociceptors. Particularly, Zymosan binds TLR2 when it is in its dimeric form with TLR6. In cultured DRGs, Zymosan has been found to directly activate nociceptors through an unknown mechanism. C. albicans can also activate nociceptors through β-glucan induced dectin-1- TRP axis, and by ATP signaling through P2X3 receptor. ATP can also be released from C. albicans to bind non-peptidergic nociceptors, but it is unclear if this leads to pain behavior. Viral pathogens, including herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2), may infect nociceptors directly to cause pain. Viral release of miRNA and ssRNA can also be sensed by TLR7 on nociceptors to cause neuronal activation. Image created with BioRender.com.