The study shows that the natural peptide LL‑37 can grab the immune‑activating molecule cGAMP and carry it into cells, boosting the body’s antiviral defenses via the STING pathway. It also finds that taking vitamin D3 or sodium butyrate can raise LL‑37 levels, potentially enhancing this effect. For DIY health enthusiasts, this suggests that supporting LL‑37 production with safe, everyday supplements might improve innate immunity, though direct use of LL‑37 itself isn’t yet a practical option.

Cyclic 2',3'-GMP-AMP (cGAMP) binds to and activates stimulator of interferon genes (STING), which then induces interferons to drive immune responses against tumors and pathogens. Exogenous cGAMP produced by infected and malignant cells and synthetic cGAMP used in immunotherapy must traverse the cell membrane to activate STING in target cells. However, as an anionic hydrophilic molecule, cGAMP is not inherently membrane permeable. Here, we show that LL-37, a human host defense peptide, can function as a transporter of cGAMP. LL-37 specifically binds cGAMP and efficiently delivers cGAMP into target cells. cGAMP transferred by LL-37 activates robust interferon responses and host antiviral immunity in a STING-dependent manner. Furthermore, we report that LL-37 inducers vitamin D₃ and sodium butyrate promote host immunity by enhancing endogenous LL-37 expression and its mediated cGAMP immune response. Collectively, our data uncover an essential role of LL-37 in innate immune activation and suggest new strategies for immunotherapy.