Work

Cutaneous nonpeptidergic neurons sense extracellular ATP to augment barrier repair and C. albicans host defense

Year: 2026

Type: article

Abstract: Cutaneous pain-sensing nociceptive neurons can directly recognize pathogen invasion and modulate the resulting host immune response. Neuronal recognition of C. albicans cell wall components is necessary and sufficient for optimal protective local type-17 immune responses. We now report a parallel neuroimmune pathway in which extracellular ATP (eATP) released from C. albicans and keratinocytes activates nonpeptidergic neurons, including Mas-related G protein-coupled receptor D ( Mrgprd )-expressing NP1 neurons, through the P2X3 ATP receptor. Ablation of NP1 neurons or P2rx3 increased C. albicans colony-forming units (CFUs), but the induction of type-17 responses was unaffected. Rather, transcriptomic analysis revealed an alteration in genes and pathways associated with barrier repair. P2rx3 −/− mice showed increased wound size and transepidermal water loss associated with a delay in barrier repair following C. albicans infection or abrasion. These data identify a neuroimmune circuit where nonpeptidergic neurons sense epidermal damage or infection through eATP and P2X3, resulting in augmented barrier repair and thus host defense.

Source: Cell Press Blue

DOI: 10.1016/j.cpblue.2026.100103