The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis
Open accessAbstract
While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors, the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane. An important outcome of cytosolic recognition is the induction of IFNalpha and IFNbeta, which are critical mediators of immunity against both bacteria and viruses. Like many intracellular pathogens, a significant fraction of the transcriptional response to Mycobacterium tuberculosis infection depends on these type I interferons, but the recognition pathways responsible remain elusive. In this work, we demonstrate that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that responds to bacterial peptidoglycan, and this event requires membrane damage that is actively inflicted by the bacterium. Unexpectedly, this recognition triggers the expression of type I interferons in a Tbk1- and Irf5-dependent manner. This response is only partially impaired by the loss of Irf3 and therefore, differs fundamentally from those stimulated by bacterial DNA, which depend entirely on this transcription factor. This difference appears to result from the unusual peptidoglycan produced by mycobacteria, which we show is a uniquely potent agonist of the Nod2/Rip2/Irf5 pathway. Thus, the Nod2 system is specialized to recognize bacteria that actively perturb host membranes and is remarkably sensitive to mycobacteria, perhaps reflecting the strong evolutionary pressure exerted by these pathogens on the mammalian immune system.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312
AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
Hornung, V., Ablasser, A., Charrel-Dennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., & Fitzgerald, K. A. (2009) · Nature · doi:10.1038/nature07725 · Cited by 2,627
Self-citationM. tuberculosis and M. leprae Translocate from the Phagolysosome to the Cytosol in Myeloid Cells
van der Wel, N., Hava, D., Houben, D., Fluitsma, D., van Zon, M., Pierson, J., Brenner, M., & Peters, P. J. (2007) · Cell · doi:10.1016/j.cell.2007.05.059 · Cited by 960
Hsu, T., Hingley-Wilson, S. M., Chen, B., Chen, M., Dai, A. Z., Morin, P. M., Marks, C. B., Padiyar, J., Goulding, C., Gingery, M., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1635213100 · Cited by 731
Wathelet, M. G., Lin, C. H., Parekh, B. S., Ronco, L. V., Howley, P. M., & Maniatis, T. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80051-9 · Cited by 730
The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling
Schoenemeyer, A., Barnes, B. J., Mancl, M. E., Latz, E., Goutagny, N., Pitha, P. M., Fitzgerald, K. A., & Golenbock, D. T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412584200 · Cited by 411 · cited 1×
“Irf5 is a related family member that has also been shown to contribute to induction of type I IFN responses triggered by TLRs, and overexpression of MyD88 has been shown to synergize with Irf5 to induce IFNb expression [47].”
BackgroundMutually dependent secretion of proteins required for mycobacterial virulence.
Fortune, S. M., Jaeger, A., Sarracino, D. A., Chase, M. R., Sassetti, C. M., Sherman, D. R., Bloom, B. R., & Rubin, E. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504922102 · Cited by 396
Self-citation
Cited by
Type I interferons in infectious disease
McNab, F., Mayer-Barber, K., Sher, A., Wack, A., & O'Garra, A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3787 · Cited by 2,780
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
Self-citationType I interferon: friend or foe?
Trinchieri, G. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20101664 · Cited by 844
Mishra, B. B., Rathinam, V. A. K., Martens, G. W., Martinot, A. J., Kornfeld, H., Fitzgerald, K. A., & Sassetti, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2474 · Cited by 571
Self-citationManzanillo, P. S., Shiloh, M. U., Portnoy, D. A., & Cox, J. S. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.03.007 · Cited by 473
Metadata
- Authors
- Pandey, A. K., Yang, Y., Jiang, Z., Fortune, S. M., Coulombe, F., Behr, M. A., Fitzgerald, K. A., Sassetti, C. M., & Kelliher, M. A.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-07-03
- Volume
- 5
- Issue
- 7
- Pages
- e1000500
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- OpenAlex
- W2158342892
- Cited by
- 292
- References
- 7
- FWCI
- 10.44
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis. https://app.cochat.ai/papers/10.1371/journal.ppat.1000500
- The paper
- Pandey, A. K., Yang, Y., Jiang, Z., Fortune, S. M., Coulombe, F., Behr, M. A., Fitzgerald, K. A., Sassetti, C. M., & Kelliher, M. A. (2009). NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1000500
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
