| First Author | Platt DJ | Year | 2021 |
| Journal | Cell Rep | Volume | 35 |
| Issue | 6 | Pages | 109113 |
| PubMed ID | 33979608 | Mgi Jnum | J:319861 |
| Mgi Id | MGI:6717074 | Doi | 10.1016/j.celrep.2021.109113 |
| Citation | Platt DJ, et al. (2021) Transferrable protection by gut microbes against STING-associated lung disease. Cell Rep 35(6):109113 |
| abstractText | STING modulates immunity by responding to bacterial and endogenous cyclic dinucleotides (CDNs). Humans and mice with STING gain-of-function mutations develop a syndrome known as STING-associated vasculopathy with onset in infancy (SAVI), which is characterized by inflammatory or fibrosing lung disease. We hypothesized that hyperresponsiveness of gain-of-function STING to bacterial CDNs might explain autoinflammatory lung disease in SAVI mice. We report that depletion of gut microbes with oral antibiotics (vancomycin, neomycin, and ampicillin [VNA]) nearly eliminates lung disease in SAVI mice, implying that gut microbes might promote STING-associated autoinflammation. However, we show that germ-free SAVI mice still develop severe autoinflammatory disease and that transferring gut microbiota from antibiotics-treated mice to germ-free animals eliminates lung inflammation. Depletion of anaerobes with metronidazole abolishes the protective effect of the VNA antibiotics cocktail, and recolonization with the metronidazole-sensitive anaerobe Bacteroides thetaiotaomicron prevents disease, confirming a protective role of a metronidazole-sensitive microbe in a model of SAVI. |
