{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:14:28Z","timestamp":1791299668066,"version":"4.1.0"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recent results indicate a significant contribution of innate immune signaling to maintain mucosal homeostasis, but the precise underlying signal transduction pathways are ill-defined. By comparative analysis of intestinal epithelial cells isolated from conventionally raised and germ-free mice, as well as animals deficient in the adaptor molecules MyD88 and TRIF, the TLR3 and TLR4, as well as the type I and III IFN receptors, we demonstrate significant TLR-mediated signaling under homeostatic conditions. Surprisingly, homeostatic expression of Reg3\u03b3 and Paneth cell enteric antimicrobial peptides critically relied on TRIF and, in part, TLR3 but was independent of IFN receptor signaling. Reduced antimicrobial peptide expression was associated with significantly lower numbers of Paneth cells and a reduced Paneth cell maturation and differentiation factor expression in TRIF mutant compared with wild-type epithelium. This phenotype was not transferred to TRIF-sufficient germ-free animals during cohousing. Low antimicrobial peptide expression in TRIF-deficient mice caused reduced immediate killing of orally administered bacteria but was not associated with significant alterations in the overall composition of the enteric microbiota. The phenotype was rapidly restored in a TRIF-independent fashion after transient epithelial damage. Our results identify TRIF signaling as a truly homeostatic pathway to maintain intestinal epithelial barrier function revealing fundamental differences in the innate immune signaling between mucosal homeostasis and tissue repair.<\/jats:p>","DOI":"10.4049\/jimmunol.1302708","type":"journal-article","created":{"date-parts":[[2014,9,11]],"date-time":"2014-09-11T04:37:15Z","timestamp":1410410235000},"page":"4223-4234","source":"Crossref","is-referenced-by-count":39,"title":["TRIF Signaling Drives Homeostatic Intestinal Epithelial Antimicrobial Peptide Expression"],"prefix":"10.1093","volume":"193","author":[{"given":"Silvia","family":"Stockinger","sequence":"first","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School , D-30625 Hannover ,","place":["Germany"]},{"name":"Institute of Animal Breeding and Genetics, University of Veterinary Medicine , 1210 Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia U","family":"Duerr","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School , D-30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Fulde","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School , D-30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamas","family":"Dolowschiak","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School , D-30625 Hannover ,","place":["Germany"]},{"name":"Institute of Microbiology, Swiss Federal Institute of Technology Z\u00fcrich , 8093 Z\u00fcrich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Pott","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School , D-30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School , D-30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Eibach","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School , D-30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"B\u00e4ckhed","sequence":"additional","affiliation":[{"name":"Wallenberg Laboratory for Cardiovascular and Metabolic Research, Sahlgrenska University Hospital, University of Gothenburg , S-405 30 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Research Institute for Microbial Diseases, Osaka University , Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Suerbaum","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School , D-30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"Brugman","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center , 2333 ZA Leiden ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias W","family":"Hornef","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School , D-30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,10,15]]},"reference":[{"key":"2025030707404480400_r1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/MOG.0b013e3283438dea","article-title":"Innate immunity in the small intestine","volume":"27","author":"Santaolalla","year":"2011","journal-title":"Curr. Opin. Gastroenterol."},{"key":"2025030707404480400_r2","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/embor.2012.96","article-title":"Innate immune signalling at the intestinal epithelium in homeostasis and disease","volume":"13","author":"Pott","year":"2012","journal-title":"EMBO Rep."},{"key":"2025030707404480400_r3","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.cell.2004.07.002","article-title":"Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis","volume":"118","author":"Rakoff-Nahoum","year":"2004","journal-title":"Cell"},{"key":"2025030707404480400_r4","doi-asserted-by":"crossref","first-page":"G1055","DOI":"10.1152\/ajpgi.00328.2004","article-title":"Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis","volume":"288","author":"Fukata","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"2025030707404480400_r5","doi-asserted-by":"crossref","first-page":"566","DOI":"10.4049\/jimmunol.179.1.566","article-title":"TLR signaling mediated by MyD88 is required for a protective innate immune response by neutrophils to Citrobacter rodentium","volume":"179","author":"Lebeis","year":"2007","journal-title":"J. Immunol."},{"key":"2025030707404480400_r6","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature05698","article-title":"Epithelial NEMO links innate immunity to chronic intestinal inflammation","volume":"446","author":"Nenci","year":"2007","journal-title":"Nature"},{"key":"2025030707404480400_r7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1073\/pnas.0405979102","article-title":"Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury","volume":"102","author":"Pull","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030707404480400_r8","doi-asserted-by":"crossref","first-page":"19967","DOI":"10.1073\/pnas.1014669107","article-title":"MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands","volume":"107","author":"Brandl","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030707404480400_r9","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.4049\/jimmunol.180.4.2588","article-title":"Loss of epithelial RelA results in deregulated intestinal proliferative\/apoptotic homeostasis and susceptibility to inflammation","volume":"180","author":"Steinbrecher","year":"2008","journal-title":"J. Immunol."},{"key":"2025030707404480400_r10","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2004.07.013","article-title":"IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer","volume":"118","author":"Greten","year":"2004","journal-title":"Cell"},{"key":"2025030707404480400_r11","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.2353\/ajpath.2006.060345","article-title":"Flagellin suppresses epithelial apoptosis and limits disease during enteric infection","volume":"169","author":"Vijay-Kumar","year":"2006","journal-title":"Am. J. Pathol."},{"key":"2025030707404480400_r12","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/ncb1500","article-title":"Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells","volume":"8","author":"Lee","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"2025030707404480400_r13","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.1179721","article-title":"Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5","volume":"328","author":"Vijay-Kumar","year":"2010","journal-title":"Science"},{"key":"2025030707404480400_r14","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.clim.2010.04.001","article-title":"Epithelial-specific blockade of MyD88-dependent pathway causes spontaneous small intestinal inflammation","volume":"136","author":"Gong","year":"2010","journal-title":"Clin. Immunol."},{"key":"2025030707404480400_r15","first-page":"3909","article-title":"Deletion of TLR5 results in spontaneous colitis in mice","volume":"117","author":"Vijay-Kumar","year":"2007","journal-title":"J. Clin. Invest."},{"key":"2025030707404480400_r16","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1084\/jem.20071108","article-title":"Homeostatic MyD88-dependent signals cause lethal inflammation in the absence of A20","volume":"205","author":"Turer","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025030707404480400_r17","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.4049\/jimmunol.181.2.1143","article-title":"Enterocyte-derived TAK1 signaling prevents epithelium apoptosis and the development of ileitis and colitis","volume":"181","author":"Kajino-Sakamoto","year":"2008","journal-title":"J. Immunol."},{"key":"2025030707404480400_r18","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nature10400","article-title":"Caspase-8 regulates TNF-\u03b1-induced epithelial necroptosis and terminal ileitis","volume":"477","author":"G\u00fcnther","year":"2011","journal-title":"Nature"},{"key":"2025030707404480400_r19","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025030707404480400_r20","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/eji.200637009","article-title":"TLR pathways and IFN-regulatory factors: to each its own","volume":"37","author":"Colonna","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"2025030707404480400_r21","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.cell.2010.01.041","article-title":"SnapShot: pathways of antiviral innate immunity","volume":"140","author":"Sun","year":"2010","journal-title":"Cell"},{"key":"2025030707404480400_r22","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1084\/jem.20050625","article-title":"Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells","volume":"203","author":"Lotz","year":"2006","journal-title":"J. Exp. Med."},{"key":"2025030707404480400_r23","doi-asserted-by":"crossref","first-page":"7944","DOI":"10.1073\/pnas.1100552108","article-title":"IFN-lambda determines the intestinal epithelial antiviral host defense","volume":"108","author":"Pott","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030707404480400_r24","doi-asserted-by":"crossref","first-page":"S96","DOI":"10.1093\/bioinformatics\/18.suppl_1.S96","article-title":"Variance stabilization applied to microarray data calibration and to the quantification of differential expression","volume":"18","author":"Huber","year":"2002","journal-title":"Bioinformatics"},{"key":"2025030707404480400_r25","volume-title":"Limma: Linear Models for Microarray Data.","author":"Smyth","year":"2005"},{"key":"2025030707404480400_r26","volume-title":"R: A Language and Environment for Statistical Computing.","author":"R DevelopmentCoreTeam","year":"2010"},{"key":"2025030707404480400_r27","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"2025030707404480400_r28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1471-2172-9-37","article-title":"Regional variations in Paneth cell antimicrobial peptide expression along the mouse intestinal tract","volume":"9","author":"Karlsson","year":"2008","journal-title":"BMC Immunol."},{"key":"2025030707404480400_r29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.pep.2006.01.014","article-title":"Refolding, purification, and characterization of human and murine RegIII proteins expressed in Escherichia coli","volume":"48","author":"Cash","year":"2006","journal-title":"Protein Expr. Purif."},{"key":"2025030707404480400_r30","doi-asserted-by":"crossref","first-page":"e70783","DOI":"10.1371\/journal.pone.0070783","article-title":"Intestinal microbiota composition of interleukin-10 deficient C57BL\/6J mice and susceptibility to Helicobacter hepaticus-induced colitis","volume":"8","author":"Yang","year":"2013","journal-title":"PLoS ONE"},{"key":"2025030707404480400_r31","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1128\/AEM.01541-09","article-title":"Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities","volume":"75","author":"Schloss","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"2025030707404480400_r32","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1093\/bioinformatics\/btr381","article-title":"UCHIME improves sensitivity and speed of chimera detection","volume":"27","author":"Edgar","year":"2011","journal-title":"Bioinformatics"},{"key":"2025030707404480400_r33","doi-asserted-by":"crossref","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy","volume":"73","author":"Wang","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"2025030707404480400_r34","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.3390\/d2071015","article-title":"TaxCollector: Modifiying current 16S rRNA databases for the rapid classification at six taxonomic levels","volume":"2","author":"Giongo","year":"2010","journal-title":"Diversity"},{"key":"2025030707404480400_r35","doi-asserted-by":"crossref","first-page":"e95","DOI":"10.1093\/nar\/gkr349","article-title":"ESPRIT-Tree: hierarchical clustering analysis of millions of 16S rRNA pyrosequences in quasilinear computational time","volume":"39","author":"Cai","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2025030707404480400_r36","volume-title":"Heatmap.","author":"Nahid","year":"2011"},{"key":"2025030707404480400_r37","volume-title":"Vegan:Community Ecology Package.","author":"Oksanen","year":"2013"},{"key":"2025030707404480400_r38","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nrmicro2546","article-title":"Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis","volume":"9","author":"Bevins","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"2025030707404480400_r39","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev-physiol-030212-183744","article-title":"Paneth cells: maestros of the small intestinal crypts","volume":"75","author":"Clevers","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"2025030707404480400_r40","doi-asserted-by":"crossref","first-page":"5219","DOI":"10.1074\/jbc.M109410200","article-title":"Activation of Paneth cell alpha-defensins in mouse small intestine","volume":"277","author":"Ayabe","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2025030707404480400_r41","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1126\/science.1127119","article-title":"Symbiotic bacteria direct expression of an intestinal bactericidal lectin","volume":"313","author":"Cash","year":"2006","journal-title":"Science"},{"key":"2025030707404480400_r42","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1084\/jem.20070563","article-title":"MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection","volume":"204","author":"Brandl","year":"2007","journal-title":"J. Exp. Med."},{"key":"2025030707404480400_r43","doi-asserted-by":"crossref","first-page":"e17996","DOI":"10.1371\/journal.pone.0017996","article-title":"Depletion of murine intestinal microbiota: effects on gut mucosa and epithelial gene expression","volume":"6","author":"Reikvam","year":"2011","journal-title":"PLoS ONE"},{"key":"2025030707404480400_r44","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1126\/science.1058709","article-title":"Commensal host-bacterial relationships in the gut","volume":"292","author":"Hooper","year":"2001","journal-title":"Science"},{"key":"2025030707404480400_r45","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1083\/jcb.148.6.1305","article-title":"Bacterial exposure induces and activates matrilysin in mucosal epithelial cells","volume":"148","author":"L\u00f3pez-Boado","year":"2000","journal-title":"J. Cell Biol."},{"key":"2025030707404480400_r46","doi-asserted-by":"crossref","first-page":"40478","DOI":"10.1074\/jbc.M007816200","article-title":"Germ-free and colonized mice generate the same products from enteric prodefensins","volume":"275","author":"Putsep","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2025030707404480400_r47","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/ni.1825","article-title":"Enteric defensins are essential regulators of intestinal microbial ecology","volume":"11","author":"Salzman","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025030707404480400_r48","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1084\/jem.20080588","article-title":"IL-17 produced by Paneth cells drives TNF-induced shock","volume":"205","author":"Takahashi","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025030707404480400_r49","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1053\/j.gastro.2011.01.004","article-title":"The epithelial barrier is maintained by in vivo tight junction expansion during pathologic intestinal epithelial shedding","volume":"140","author":"Marchiando","year":"2011","journal-title":"Gastroenterology"},{"key":"2025030707404480400_r50","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1083\/jcb.200902153","article-title":"Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo","volume":"189","author":"Marchiando","year":"2010","journal-title":"J. Cell Biol."},{"key":"2025030707404480400_r51","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2013.07.004","article-title":"The intestinal crypt, a prototype stem cell compartment","volume":"154","author":"Clevers","year":"2013","journal-title":"Cell"},{"key":"2025030707404480400_r52","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1083\/jcb.200704152","article-title":"Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium","volume":"178","author":"Bastide","year":"2007","journal-title":"J. Cell Biol."},{"key":"2025030707404480400_r53","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0092-8674(02)01015-2","article-title":"Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB\/ephrinB","volume":"111","author":"Batlle","year":"2002","journal-title":"Cell"},{"key":"2025030707404480400_r54","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1053\/j.gastro.2007.05.020","article-title":"SOX9 is required for the differentiation of paneth cells in the intestinal epithelium","volume":"133","author":"Mori-Akiyama","year":"2007","journal-title":"Gastroenterology"},{"key":"2025030707404480400_r55","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0889-8553(21)00207-7","article-title":"Current concepts of the etiology and pathogenesis of ulcerative colitis and Crohn\u2019s disease","volume":"24","author":"Sartor","year":"1995","journal-title":"Gastroenterol. Clin. North Am."},{"key":"2025030707404480400_r56","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.immuni.2009.08.009","article-title":"Immune responses to the microbiota at the intestinal mucosal surface","volume":"31","author":"Duerkop","year":"2009","journal-title":"Immunity"},{"key":"2025030707404480400_r57","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nri2707","article-title":"Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function","volume":"10","author":"Abreu","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"2025030707404480400_r58","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.immuni.2010.02.012","article-title":"Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases","volume":"32","author":"Dupaul-Chicoine","year":"2010","journal-title":"Immunity"},{"key":"2025030707404480400_r59","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/nm.2143","article-title":"ERK activation drives intestinal tumorigenesis in Apc(min\/+) mice","volume":"16","author":"Lee","year":"2010","journal-title":"Nat. Med."},{"key":"2025030707404480400_r60","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1126\/science.1140488","article-title":"Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88","volume":"317","author":"Rakoff-Nahoum","year":"2007","journal-title":"Science"},{"key":"2025030707404480400_r61","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1084\/jem.20100199","article-title":"MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18","volume":"207","author":"Salcedo","year":"2010","journal-title":"J. Exp. Med."},{"key":"2025030707404480400_r62","doi-asserted-by":"crossref","first-page":"37570","DOI":"10.1074\/jbc.M110.158394","article-title":"TRIF mediates Toll-like receptor 5-induced signaling in intestinal epithelial cells","volume":"285","author":"Choi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2025030707404480400_r63","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s00535-004-1492-9","article-title":"MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis","volume":"40","author":"Araki","year":"2005","journal-title":"J. Gastroenterol."},{"key":"2025030707404480400_r64","doi-asserted-by":"crossref","first-page":"15058","DOI":"10.1073\/pnas.0808216105","article-title":"Opposing functions of IKKbeta during acute and chronic intestinal inflammation","volume":"105","author":"Eckmann","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030707404480400_r65","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.smim.2006.10.002","article-title":"Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota","volume":"19","author":"Smith","year":"2007","journal-title":"Semin. Immunol."},{"key":"2025030707404480400_r66","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1126\/science.291.5505.881","article-title":"Molecular analysis of commensal host-microbial relationships in the intestine","volume":"291","author":"Hooper","year":"2001","journal-title":"Science"},{"key":"2025030707404480400_r67","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1084\/jem.20081370","article-title":"TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events","volume":"205","author":"Cavassani","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025030707404480400_r68","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nature10072","article-title":"Detection of prokaryotic mRNA signifies microbial viability and promotes immunity","volume":"474","author":"Sander","year":"2011","journal-title":"Nature"},{"key":"2025030707404480400_r69","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.immuni.2013.02.024","article-title":"Double-stranded RNA of intestinal commensal but not pathogenic bacteria triggers production of protective interferon-\u03b2","volume":"38","author":"Kawashima","year":"2013","journal-title":"Immunity"},{"key":"2025030707404480400_r70","doi-asserted-by":"crossref","first-page":"e10250","DOI":"10.1371\/journal.pone.0010250","article-title":"Murine toll-like receptor 2 activation induces type I interferon responses from endolysosomal compartments","volume":"5","author":"Dietrich","year":"2010","journal-title":"PLoS ONE"},{"key":"2025030707404480400_r71","doi-asserted-by":"crossref","first-page":"e33299","DOI":"10.1371\/journal.pone.0033299","article-title":"Both TLR2 and TRIF contribute to interferon-\u03b2 production during Listeria infection","volume":"7","author":"Aubry","year":"2012","journal-title":"PLoS ONE"},{"key":"2025030707404480400_r72","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1128\/IAI.00890-12","article-title":"TRIF mediates Toll-like receptor 2-dependent inflammatory responses to Borrelia burgdorferi","volume":"81","author":"Petnicki-Ocwieja","year":"2013","journal-title":"Infect. Immun."},{"key":"2025030707404480400_r73","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1038\/cdd.2012.22","article-title":"dsRNA induces apoptosis through an atypical death complex associating TLR3 to caspase-8","volume":"19","author":"Estornes","year":"2012","journal-title":"Cell Death Differ."},{"key":"2025030707404480400_r74","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.4049\/jimmunol.173.5.3320","article-title":"Signaling of apoptosis through TLRs critically involves toll\/IL-1 receptor domain-containing adapter inducing IFN-beta, but not MyD88, in bacteria-infected murine macrophages","volume":"173","author":"Ruckdeschel","year":"2004","journal-title":"J. Immunol."},{"key":"2025030707404480400_r75","doi-asserted-by":"crossref","first-page":"418","DOI":"10.4049\/jimmunol.1202756","article-title":"TLR3, TRIF, and caspase 8 determine double-stranded RNA-induced epithelial cell death and survival in vivo","volume":"190","author":"McAllister","year":"2013","journal-title":"J. Immunol."},{"key":"2025030707404480400_r76","doi-asserted-by":"crossref","first-page":"e1002670","DOI":"10.1371\/journal.ppat.1002670","article-title":"Age-dependent TLR3 expression of the intestinal epithelium contributes to rotavirus susceptibility","volume":"8","author":"Pott","year":"2012","journal-title":"PLoS Pathog."},{"key":"2025030707404480400_r77","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nature10273","article-title":"FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation","volume":"477","author":"Welz","year":"2011","journal-title":"Nature"},{"key":"2025030707404480400_r78","doi-asserted-by":"crossref","first-page":"31268","DOI":"10.1074\/jbc.M113.462341","article-title":"Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL","volume":"288","author":"Kaiser","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2025030707404480400_r79","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nature07416","article-title":"A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells","volume":"456","author":"Cadwell","year":"2008","journal-title":"Nature"},{"key":"2025030707404480400_r80","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.cell.2008.07.021","article-title":"XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease","volume":"134","author":"Kaser","year":"2008","journal-title":"Cell"},{"key":"2025030707404480400_r81","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature12599","article-title":"Paneth cells as a site of origin for intestinal inflammation","volume":"503","author":"Adolph","year":"2013","journal-title":"Nature"},{"key":"2025030707404480400_r82","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1084\/jem.20110547","article-title":"Host innate recognition of an intestinal bacterial pathogen induces TRIF-dependent protective immunity","volume":"208","author":"Sotolongo","year":"2011","journal-title":"J. Exp. Med."},{"key":"2025030707404480400_r83","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nature01520","article-title":"Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin","volume":"422","author":"Salzman","year":"2003","journal-title":"Nature"},{"key":"2025030707404480400_r84","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1126\/science.286.5437.113","article-title":"Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense","volume":"286","author":"Wilson","year":"1999","journal-title":"Science"},{"key":"2025030707404480400_r85","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/77783","article-title":"Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria","volume":"1","author":"Ayabe","year":"2000","journal-title":"Nat. Immunol."},{"key":"2025030707404480400_r86","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1126\/science.1172747","article-title":"Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism","volume":"325","author":"Slack","year":"2009","journal-title":"Science"},{"key":"2025030707404480400_r87","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1084\/jem.20120504","article-title":"Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice","volume":"209","author":"Ubeda","year":"2012","journal-title":"J. Exp. Med."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/193\/8\/4223\/62228133\/1302708.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/193\/8\/4223\/62228133\/1302708.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T03:11:29Z","timestamp":1741317089000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/193\/8\/4223\/7960385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10]]},"references-count":87,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,10,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1302708","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,10]]},"published":{"date-parts":[[2014,10]]}}}