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Transferrable protection by gut microbes against STING-associated lung disease
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 disea...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477380/ https://www.ncbi.nlm.nih.gov/pubmed/33979608 http://dx.doi.org/10.1016/j.celrep.2021.109113 |
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author | Platt, Derek J. Lawrence, Dylan Rodgers, Rachel Schriefer, Lawrence Qian, Wei Miner, Cathrine A. Menos, Amber M. Kennedy, Elizabeth A. Peterson, Stefan T. Stinson, W. Alexander Baldridge, Megan T. Miner, Jonathan J. |
author_facet | Platt, Derek J. Lawrence, Dylan Rodgers, Rachel Schriefer, Lawrence Qian, Wei Miner, Cathrine A. Menos, Amber M. Kennedy, Elizabeth A. Peterson, Stefan T. Stinson, W. Alexander Baldridge, Megan T. Miner, Jonathan J. |
author_sort | Platt, Derek J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8477380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-84773802021-09-28 Transferrable protection by gut microbes against STING-associated lung disease Platt, Derek J. Lawrence, Dylan Rodgers, Rachel Schriefer, Lawrence Qian, Wei Miner, Cathrine A. Menos, Amber M. Kennedy, Elizabeth A. Peterson, Stefan T. Stinson, W. Alexander Baldridge, Megan T. Miner, Jonathan J. Cell Rep Article 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. 2021-05-11 /pmc/articles/PMC8477380/ /pubmed/33979608 http://dx.doi.org/10.1016/j.celrep.2021.109113 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Platt, Derek J. Lawrence, Dylan Rodgers, Rachel Schriefer, Lawrence Qian, Wei Miner, Cathrine A. Menos, Amber M. Kennedy, Elizabeth A. Peterson, Stefan T. Stinson, W. Alexander Baldridge, Megan T. Miner, Jonathan J. Transferrable protection by gut microbes against STING-associated lung disease |
title | Transferrable protection by gut microbes against STING-associated lung disease |
title_full | Transferrable protection by gut microbes against STING-associated lung disease |
title_fullStr | Transferrable protection by gut microbes against STING-associated lung disease |
title_full_unstemmed | Transferrable protection by gut microbes against STING-associated lung disease |
title_short | Transferrable protection by gut microbes against STING-associated lung disease |
title_sort | transferrable protection by gut microbes against sting-associated lung disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477380/ https://www.ncbi.nlm.nih.gov/pubmed/33979608 http://dx.doi.org/10.1016/j.celrep.2021.109113 |
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