2022 journal article
LL-37 transports immunoreactive cGAMP to activate STING signaling and enhance interferon-mediated host antiviral immunity
CELL REPORTS, 39(9).
MeSH headings : Antiviral Restriction Factors / immunology; Cathelicidins / immunology; Humans; Immunity, Innate; Interferons / immunology; Membrane Proteins / metabolism; Nucleotides, Cyclic
TL;DR:
LL-37, a human host defense peptide, can function as a transporter of cGAMP and activates robust interferon responses and host antiviral immunity in a STING-dependent manner and suggests new strategies for immunotherapy.
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open access via www.cell.com (publisher PDF)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: July 11, 2022
<h2>Summary</h2> 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 D<sub>3</sub> 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.