Mechanisms of fungal pathogenic DNA-activated STING pathway in biofilms and its implication in dental caries onset.

Dental caries, a prevalent oral disease, has long been attributed primarily to bacteria, but emerging evidence highlights the critical role of fungi in its pathogenesis. Fungal biofilms, predominantly Candida albicans, release extracellular DNA (eDNA) and DNA-carrying extracellular vesicles (EVs). Together with bacterial eDNA, these form the biofilm matrix and can activate the host cGAS-STING signaling pathway. This review systematically elaborates on the molecular architecture and biological functions of the cGAS-STING pathway, comparing mechanistic differences in its activation by viral, bacterial, and fungal DNA. It further explores direct and indirect modes of STING pathway activation by fungal eDNA and EV-carried DNA, along with their immunoregulatory roles. Specifically, it discusses the interactive mechanisms between fungal biofilms and STING activation in root caries onset, emphasizing the dual effects of STING-mediated immune responses-enhancing antifungal immunity while potentially exacerbating tissue damage via excessive inflammation. Finally, this review outlines current knowledge gaps and future research directions, aiming to provide novel insights for precision prevention and treatment of dental caries.