{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNOD2 is a cytosolic innate immune receptor that detects the bacterial cell wall component muramyl dipeptide (MDP) – a conserved motif present in all bacteria – and thereby initiates a cascade of inflammatory and antimicrobial responses. Upon recognition of MDP, NOD2 activates key signaling pathways such as nuclear factor‐κB (NF‑κB), mitogen‑activated protein kinases (MAPKs) and, in some contexts, interferon‐regulatory factors. These cascades lead to the production of inflammatory cytokines, chemokines, and antimicrobial peptides, as well as the modulation of adaptive immunity. In addition, NOD2 interacts with downstream adaptor molecules like RIP2 and regulatory proteins including Erbin and XIAP to fine‑tune these signaling events."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role as a microbial sensor, NOD2 is a central coordinator of downstream defensive processes. Its activation promotes autophagy by recruiting key autophagic proteins (such as ATG16L1) to sites of bacterial entry, thereby facilitating the encapsulation and clearance of invading pathogens. Furthermore, NOD2 mediates the processing and secretion of pro‑inflammatory cytokines like interleukin‑1β through caspase‑1 activation and drives both innate and adaptive immune responses by modulating T‐helper cell polarization. These functions are mediated through a network of interactions with other innate receptors and signaling intermediates, ensuring a rapid and appropriate response to infection."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of NOD2 signaling is strongly implicated in inflammatory disorders such as Crohn’s disease and may compromise mucosal barrier integrity, leading to abnormal gut microbiota composition and increased susceptibility to bacterial as well as viral infections. Impaired NOD2 function, whether through genetic mutations or altered receptor–ligand interactions, results in defective antimicrobial peptide secretion, abnormal inflammatory cytokine profiles, and improper recruitment of immune effector cells. Such disruptions contribute to the breakdown of intestinal homeostasis and facilitate chronic inflammation, highlighting NOD2’s critical role as a master regulator of both immune defense and tolerance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stephen E Girardin, Ivo G Boneca, Jérôme Viala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C200651200"}], "href": "https://doi.org/10.1074/jbc.C200651200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12527755"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12527755"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Anne-Laure Pauleau, Peter J Murray "}, {"type": "b", "children": [{"type": "t", "text": "Role of nod2 in the response of macrophages to toll-like receptor agonists."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.21.7531-7539.2003"}], "href": "https://doi.org/10.1128/MCB.23.21.7531-7539.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14560001"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14560001"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tomohiro Watanabe, Atsushi Kitani, Peter J Murray, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni1092"}], "href": "https://doi.org/10.1038/ni1092"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15220916"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15220916"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Koichi S Kobayashi, Mathias Chamaillard, Yasunori Ogura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1104911"}], "href": "https://doi.org/10.1126/science.1104911"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15692051"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15692051"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shin Maeda, Li-Chung Hsu, Hongjun Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1103685"}], "href": "https://doi.org/10.1126/science.1103685"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15692052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15692052"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jong-Hwan Park, Yun-Gi Kim, Christine McDonald, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.178.4.2380"}], "href": "https://doi.org/10.4049/jimmunol.178.4.2380"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17277144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17277144"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sylvie Legrand-Poels, Gaelle Kustermans, Françoise Bex, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of Nod2-dependent NF-kappaB signaling by the actin cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.03424"}], "href": "https://doi.org/10.1242/jcs.03424"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17356065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17356065"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Qilin Pan, John Mathison, Colleen Fearns, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MDP-induced interleukin-1beta processing requires Nod2 and CIAS1/NALP3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.1006627"}], "href": "https://doi.org/10.1189/jlb.1006627"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17403772"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17403772"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Gerben Ferwerda, Bart Jan Kullberg, Dirk J de Jong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mycobacterium paratuberculosis is recognized by Toll-like receptors and NOD2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.0307147"}], "href": "https://doi.org/10.1189/jlb.0307147"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17652449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17652449"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yibin Yang, Catherine Yin, Amit Pandey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M703079200"}], "href": "https://doi.org/10.1074/jbc.M703079200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17947236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17947236"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yun-Gi Kim, Jong-Hwan Park, Michael H Shaw, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2007.12.012"}], "href": "https://doi.org/10.1016/j.immuni.2007.12.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18261938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18261938"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Noemí Marina-García, Luigi Franchi, Yun-Gi Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1 activation via cryopyrin/NLRP3 independently of Nod2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.180.6.4050"}], "href": "https://doi.org/10.4049/jimmunol.180.6.4050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18322214"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18322214"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Philippe M LeBlanc, Garabet Yeretssian, Nancy Rutherford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caspase-12 modulates NOD signaling and regulates antimicrobial peptide production and mucosal immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2008.02.004"}], "href": "https://doi.org/10.1016/j.chom.2008.02.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18329614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18329614"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Li-Chung Hsu, Syed R Ali, Shauna McGillivray, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0802726105"}], "href": "https://doi.org/10.1073/pnas.0802726105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18511561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18511561"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Maziar Divangahi, Serge Mostowy, François Coulombe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOD2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.181.10.7157"}], "href": "https://doi.org/10.4049/jimmunol.181.10.7157"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18981137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18981137"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Noemí Marina-García, Luigi Franchi, Yun-Gi Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clathrin- and dynamin-dependent endocytic pathway regulates muramyl dipeptide internalization and NOD2 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0802197"}], "href": "https://doi.org/10.4049/jimmunol.0802197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19299732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19299732"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Kenichi Shimada, Shuang Chen, Paul W Dempsey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1000379"}], "href": "https://doi.org/10.1371/journal.ppat.1000379"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19360122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19360122"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Petr Hruz, Annelies S Zinkernagel, Gabriela Jenikova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOD2 contributes to cutaneous defense against Staphylococcus aureus through alpha-toxin-dependent innate immune activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0904958106"}], "href": "https://doi.org/10.1073/pnas.0904958106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19541630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19541630"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Ahmed Sabbah, Te Hung Chang, Rosalinda Harnack, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of innate immune antiviral responses by Nod2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.1782"}], "href": "https://doi.org/10.1038/ni.1782"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19701189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19701189"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Simone Lipinski, Andreas Till, Christian Sina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DUOX2-derived reactive oxygen species are effectors of NOD2-mediated antibacterial responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.050690"}], "href": "https://doi.org/10.1242/jcs.050690"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19759286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19759286"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Tanja Petnicki-Ocwieja, Tomas Hrncir, Yuen-Joyce Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nod2 is required for the regulation of commensal microbiota in the intestine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0907722106"}], "href": "https://doi.org/10.1073/pnas.0907722106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19805227"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19805227"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Leonardo H Travassos, Leticia A M Carneiro, Mahendrasingh Ramjeet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.1823"}], "href": "https://doi.org/10.1038/ni.1823"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19898471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19898471"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Claudia Toma, Naomi Higa, Yukiko Koizumi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pathogenic Vibrio activate NLRP3 inflammasome via cytotoxins and TLR/nucleotide-binding oligomerization domain-mediated NF-kappa B signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0903536"}], "href": "https://doi.org/10.4049/jimmunol.0903536"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20348425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20348425"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Justine T Tigno-Aranjuez, John M Asara, Derek W Abbott "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1964410"}], "href": "https://doi.org/10.1101/gad.1964410"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21123652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21123652"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Ateequr Rehman, Christian Sina, Olga Gavrilova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nod2 is essential for temporal development of intestinal microbial communities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gut (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/gut.2010.216259"}], "href": "https://doi.org/10.1136/gut.2010.216259"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21421666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21421666"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yun-Gi Kim, Nobuhiko Kamada, Michael H Shaw, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Nod2 sensor promotes intestinal pathogen eradication via the chemokine CCL2-dependent recruitment of inflammatory monocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2011.04.013"}], "href": "https://doi.org/10.1016/j.immuni.2011.04.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21565531"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21565531"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Ulrich Meinzer, Frederick Barreau, Sophie Esmiol-Welterlin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Yersinia pseudotuberculosis effector YopJ subverts the Nod2/RICK/TAK1 pathway and activates caspase-1 to induce intestinal barrier dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2012.02.009"}], "href": "https://doi.org/10.1016/j.chom.2012.02.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22520462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22520462"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Rune Busk Damgaard, Ueli Nachbur, Monica Yabal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2012.04.014"}], "href": "https://doi.org/10.1016/j.molcel.2012.04.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22607974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22607974"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Aurélie Couturier-Maillard, Thomas Secher, Ateequr Rehman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI62236"}], "href": "https://doi.org/10.1172/JCI62236"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23281400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23281400"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Dong-Jae Kim, Jong-Hwan Park, Luigi Franchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Cag pathogenicity island and interaction between TLR2/NOD2 and NLRP3 regulate IL-1β production in Helicobacter pylori infected dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.201243281"}], "href": "https://doi.org/10.1002/eji.201243281"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23818043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23818043"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Norihiro Nakamura, Jennie R Lill, Qui Phung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endosomes are specialized platforms for bacterial sensing and NOD2 signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature13133"}], "href": "https://doi.org/10.1038/nature13133"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24695226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24695226"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Giulia Nigro, Raffaella Rossi, Pierre-Henri Commere, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2014.05.003"}], "href": "https://doi.org/10.1016/j.chom.2014.05.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24882705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24882705"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Deepshika Ramanan, Mei San Tang, Rowann Bowcutt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2014.06.015"}], "href": "https://doi.org/10.1016/j.immuni.2014.06.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25088769"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25088769"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Qin Zhang, Ying Pan, Ruiqing Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Commensal bacteria direct selective cargo sorting to promote symbiosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.3233"}], "href": "https://doi.org/10.1038/ni.3233"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26237551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26237551"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "A Marijke Keestra-Gounder, Mariana X Byndloss, Núbia Seyffert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOD1 and NOD2 signalling links ER stress with inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature17631"}], "href": "https://doi.org/10.1038/nature17631"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27007849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27007849"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Deepshika Ramanan, Rowann Bowcutt, Soo Ching Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Helminth infection promotes colonization resistance via type 2 immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aaf3229"}], "href": "https://doi.org/10.1126/science.aaf3229"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27080105"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27080105"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Frederico R C Costa, Marcela C S Françozo, Gabriela G de Oliveira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gut microbiota translocation to the pancreatic lymph nodes triggers NOD2 activation and contributes to T1D onset."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20150744"}], "href": "https://doi.org/10.1084/jem.20150744"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27325889"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27325889"}]}]}]}