Limiting cholesterol biosynthetic flux engages type I IFN signaling in a STING-dependent manner

ABSTRACT: Cellular lipid requirements are achieved through a combination of biosynthesis and import programs. Using isotope tracer analysis, we show that type I interferon (IFN) signaling rapidly shifts the balance of these programs by decreasing synthesis and increasing import of cholesterol and long chain fatty acids. Genetically enforcing this metabolic shift in macrophages is sufficient to render mice resistant to viral challenge, demonstrating the importance of reprogramming the balance of these two metabolic pathways in vivo. Unexpectedly, mechanistic studies reveal that limiting flux through the cholesterol biosynthetic pathway spontaneously engages a type I IFN response in a STING-dependent manner. The upregulation of type I IFNs was traced to a decrease in the pool size of synthesized chole

ORGANISM(S): Homo sapiens

SUBMITTER: Steven Bensinger 

PROVIDER: E-GEOD-73942 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress