ArticlePLoS pathogens2009
NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
158 citing papers in PubMed, 1 synthesis or guideline pooled it, 283 citations in OpenAlex.
- Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.Nature genetics · 2011Pooled it
- Oral delivery of oligomeric procyanidins in Apple Poly® enhances type I IFN responses in vivo.Journal of leukocyte biology · 2014Trial
- Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes.Journal of leukocyte biology · 2013Trial
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- Host-pathogen interactions in tuberculosis: from immunological mechanisms to translational applications.Cell insight · 2026Review
- Purine and pyrimidine-based bacterial cyclic dinucleotides egress the phagosome and activate the innate immune sensor STING.Immunity · 2026Article
- Article
- NOD2 activation reprograms infiltrating inflammatory monocytes in the Zika virus infected CNS to maintain neural correlates of learning and memory.bioRxiv : the preprint server for biology · 2026Article
- Mycobacterial ESAT-6 triggers cGAS-STING pathway via the GSDMD-NT dependent mitochondria dysfunction.Virulence · 2025Article
- Nucleotide-Binding Oligomerization Domain 2 in Signaling, Immunity, and Mycobacterial Infection.Immunity, inflammation and disease · 2025Review
- Interferons in health and disease.Cell · 2025Review
- The dual role of type I interferons in bacterial infections: from immune defense to pathogenesis.mBio · 2025Review
- For Better or Worse: Type I Interferon Responses in Bacterial Infection.Pathogens (Basel, Switzerland) · 2025Review
- An essential role for TASL in mouse autoimmune pathogenesis and Toll-like receptor signaling.Nature communications · 2025Article
- Differential Host Gene Expression in Response to Infection by DifferentMicroorganisms · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Mutual regulations betweenFrontiers in immunology · 2024Review
- Mycobacterium tuberculosis and its clever approaches to escape the deadly macrophage.World journal of microbiology & biotechnology · 2023Review
- Microbial cues stimulate linear growth in undernourished mice.Nature reviews. Gastroenterology & hepatology · 2023Article
- Transcriptomic Analysis of Mycobacterial Infected Macrophages Reveals a High MOI Specific Type I IFN Signaling.Infection and immunity · 2023Article
98 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
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.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.