Transferrable protection by gut microbes against STING-associated lung disease

• DOI: 10.1016/j.celrep.2021.109113
• Publication Date: 2021-05-11T15:56:30Z
• Authors: Derek J. Platt; Dylan Lawrence; Rachel Rodgers; Lawrence Schriefer; Wei Qian; Cathrine A. Miner; Amber M. Menos; Elizabeth A. Kennedy; Stefan T. Peterson; W. Alexander Stinson; Megan T. Baldridge; Jonathan J. Miner
• Keywords: Sting

STING modulates immunity by responding to bacterial and endogenous cyclic dinucleotides (CDNs). Humans mice with gain-of-function mutations develop a syndrome known as STING-associated vasculopathy onset in infancy (SAVI), which is characterized inflammatory or fibrosing lung disease. We hypothesized that hyperresponsiveness of CDNs might explain autoinflammatory disease SAVI mice. report depletion gut microbes oral antibiotics (vancomycin, neomycin, ampicillin [VNA]) nearly eliminates mice, implying promote autoinflammation. However, we show germ-free still severe transferring microbiota from antibiotics-treated animals inflammation. Depletion anaerobes metronidazole abolishes the protective effect VNA cocktail, recolonization metronidazole-sensitive anaerobe Bacteroides thetaiotaomicron prevents disease, confirming role microbe model SAVI.