The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Mycobacterium Tuberculosis Activates the DNA-Dependent Cytosolic Surveillance Pathway within Macrophages
Open accessAbstract
Summary Cytosolic bacterial pathogens activate the cytosolic surveillance pathway (CSP) and induce innate immune responses, but how the host detects vacuolar pathogens like Mycobacterium tuberculosis is poorly understood. We show that M. tuberculosis also initiates the CSP upon macrophage infection via limited perforation of the phagosome membrane mediated by the ESX-1 secretion system. Although the bacterium remains within the phagosome, this permeabilization results in phagosomal and cytoplasmic mixing and allows extracellular mycobacterial DNA to access host cytosolic receptors, thus blurring the distinction between “vacuolar” and “cytosolic” pathogens. Activation of cytosolic receptors induces signaling through the STING/TBK1/IRF3 axis, resulting in IFN-β production. Surprisingly, IRF3−/− mice, which cannot respond to cytosolic DNA, are resistant to long-term M. tuberculosis infection, suggesting that the CSP promotes M. tuberculosis infection. Thus, cytosolic sensing of mycobacterial DNA plays a key role in M. tuberculosis pathogenesis and likely contributes to the high type I IFN signature in tuberculosis.
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Citations
Cites
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Ishikawa, H., Ma, Z., & Barber, G. N. (2009) · Nature · doi:10.1038/nature08476 · Cited by 2,759 · cited 5×
“BMDMs were obtained from the following mouse strains:MYD88 / /TRIF / (Barbalat et al., 2009); TREX1 / (Stetson et al., 2008); STING / (Ishikawa et al., 2009); TNFR1 / and TBK1 / /TNFR1 / (Ishii et al., 2008); and IFNAR1 / , IRF1 / , IRF3 / , IRF5 / , and IRF7 / (Takaoka et al., 2007).”
BackgroundInfluentialIKKε and TBK1 are essential components of the IRF3 signaling pathway
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Extracellular DNA Required for Bacterial Biofilm Formation
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A Lentiviral RNAi Library for Human and Mouse Genes Applied to an Arrayed Viral High-Content Screen
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DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response
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IFI16 is an innate immune sensor for intracellular DNA
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STING is a direct innate immune sensor of cyclic di-GMP
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Gut inflammation provides a respiratory electron acceptor for Salmonella
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Cited by
Autophagy in infection, inflammation and immunity
Deretic, V., Saitoh, T., & Akira, S. (2013) · Nature Reviews Immunology · doi:10.1038/nri3532 · Cited by 1,919
Pai, M., Behr, M. A., Dowdy, D., Dheda, K., Divangahi, M., Boehme, C. C., Ginsberg, A., Swaminathan, S., Spigelman, M., Getahun, H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.76 · Cited by 1,270
The cGAS-cGAMP-STING Pathway of Cytosolic DNA Sensing and Signaling
Cai, X., Chiu, Y.-H., & Chen, Z. J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.040 · Cited by 988
Watson, R. O., Manzanillo, P. S., & Cox, J. S. (2012) · Cell · doi:10.1016/j.cell.2012.06.040 · Cited by 755
Self-citationPaludan, S. R., & Bowie, A. G. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.004 · Cited by 759
Metadata
- Authors
- Manzanillo, P. S., Shiloh, M. U., Portnoy, D. A., & Cox, J. S.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 11
- Issue
- 5
- Pages
- 469-480
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W1984355221
- Cited by
- 473
- References
- 52
- FWCI
- 25.29
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Manzanillo, P. S., Shiloh, M. U., Portnoy, D. A., & Cox, J. S. (2012). Mycobacterium Tuberculosis Activates the DNA-Dependent Cytosolic Surveillance Pathway within Macrophages. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2012.03.007
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
