<i>Borrelia burgdorferi</i>c-di-AMP induces type I IFN response in macrophage through the activation of STING signaling pathway

Abstract Lyme disease (LD) which is caused by the spirochete Borrelia burgdorferi (Bb) poses a global health threat. Bb infection induces type I IFN response that associated with arthritis and other symptoms. However, ligands, PAMPs, signaling pathways production are poorly characterized. Stimulator of Interferon Genes (STING) pathway an intracellular surveillance detects c-di-nucleotides (CDNs) produced pathogens through STING production. produces CDNs hence it has potential to activate pathway. In this study, role c-di-AMP in elicitation was elucidated. The RAW cell line infected activation measured detecting downstream proteins (pSTING, pTBK1, pIRF3 &amp; pNF-κB), proinflammatory cytokines (IL6, TNF-α) Type (IFN-β) using ELISA, western blotting, immunostaining, Luciferase Reporter assay. macrophage results mediated response. induction level dependent on as mutant strain producing higher induced cytokine Interestingly, released into BSK-II medium during culture could also stimulate protein KO showed reduction IFN-β. conclusion, our show Bb-produced major PAMP triggers interferon