2,068
Views
61
CrossRef citations to date
0
Altmetric
Review

The innate immune system and inflammatory bowel disease

&
Pages 24-33 | Received 09 Sep 2014, Accepted 13 Sep 2014, Published online: 19 Dec 2014

References

  • RBSartor. Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 2006;3:390–407.
  • LJostins, SRipke, RKWeersma, RHDuerr, DPMcGovern, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012;491:119–24.
  • JADaniels, HMLederman, AMaitra, EAMontgomery. Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review. Am J Surg Pathol 2007;31:1800–12.
  • HHUhlig. Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease. Gut 2013;62:1795–805.
  • DJMarks, KMiyagi, FZRahman, MNovelli, SLBloom, AWSegal. Inflammatory bowel disease in CGD reproduces the clinicopathological features of Crohn’s disease. Am J Gastroenterol 2009;104:117–24.
  • GMDamen, JHvan Krieken, EHoppenreijs, Evan Os, JJTolboom, AWarris, et al. Overlap, common features, and essential differences in pediatric granulomatous inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2010;51:690–7.
  • HKumar, TKawai, SAkira. Toll-like receptors and innate immunity. Biochem Biophys Res Commun 2009;388:621–5.
  • KTakeda, TKaisho, SAkira. Toll-like receptors. Annu Rev Immunol 2003;21:335–76.
  • AFMcGettrick, LAO’Neill. Localisation and trafficking of Toll-like receptors: an important mode of regulation. Curr Opin Immunol 2010;22:20–7.
  • ASVamadevan, MFukata, ETArnold, LSThomas, DHsu, MTAbreu. Regulation of Toll-like receptor 4-associated MD-2 in intestinal epithelial cells: a comprehensive analysis. Innate Immun 2010;16:93–103.
  • ECario, DKPodolsky. Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000;68:7010–17.
  • MTAbreu. Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat Rev Immunol 2010;10:131–44.
  • FYLiew, DXu, EKBrint, LAO’Neill. Negative regulation of toll-like receptor-mediated immune responses. Nat Rev Immunol 2005;5:446–58.
  • LFrolova, PDrastich, PRossmann, KKlimesova, HTlaskalova-Hogenova. Expression of Toll-like receptor 2 (TLR2), TLR4, and CD14 in biopsy samples of patients with inflammatory bowel diseases: upregulated expression of TLR2 in terminal ileum of patients with ulcerative colitis. J Histochem Cytochem 2008;56:267–74.
  • MHausmann, SKiessling, SMestermann, GWebb, TSpottl, TAndus, et al. Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology 2002;122:1987–2000.
  • NCArbour, ELorenz, BCSchutte, JZabner, JNKline, MJones, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 2000;25:187–91.
  • DFranchimont, SVermeire, HEl Housni, MPierik, KVan Steen, TGustot, et al. Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis. Gut 2004;53:987–92.
  • HPTorok, JGlas, LTonenchi, TMussack, CFolwaczny. Polymorphisms of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis. Clin Immunol 2004;112:85–91.
  • BLBrowning, CHuebner, IPetermann, RBGearry, MLBarclay, ANShelling, et al. Has toll-like receptor 4 been prematurely dismissed as an inflammatory bowel disease gene? Association study combined with meta-analysis shows strong evidence for association. Am J Gastroenterol 2007;102:2504–12.
  • SVSitaraman, JMKlapproth, DAMoore3rd, CLanders, STargan, IRWilliams, et al. Elevated flagellin-specific immunoglobulins in Crohn’s disease. Am J Physiol Gastrointest Liver Physiol 2005;288:G403–6.
  • MJLodes, YCong, COElson, RMohamath, CJLanders, SRTargan, et al. Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest 2004;113:1296–306.
  • SRTargan, CJLanders, HYang, MJLodes, YCong, KAPapadakis, et al. Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn’s disease. Gastroenterology 2005;128:2020–8.
  • AAraki, TKanai, TIshikura, SMakita, KUraushihara, RIiyama, et al. MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis. J Gastroenterol 2005;40:16–23.
  • SRakoff-Nahoum, JPaglino, FEslami-Varzaneh, SEdberg, RMedzhitov. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004;118:229–41.
  • MFukata, KSMichelsen, REri, LSThomas, BHu, KLukasek, et al. Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis. Am J Physiol Gastrointest Liver Physiol 2005;288:G1055–65.
  • MJAsquith, OBoulard, FPowrie, KJMaloy. Pathogenic and protective roles of MyD88 in leukocytes and epithelial cells in mouse models of inflammatory bowel disease. Gastroenterology 2010;139:519–29. 529 e1-2.
  • CGarlanda, FRiva, NPolentarutti, CBuracchi, MSironi, MDe Bortoli, et al. Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family. Proc Natl Acad Sci USA 2004;101:3522–6.
  • HXiao, MFGulen, JQin, JYao, KBulek, DKish, et al. The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis. Immunity 2007;26:461–75.
  • MStahl, JRies, JVermeulen, HYang, HPSham, SMCrowley, et al. A novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection. PLoS Pathog 2014;10:e1004264.
  • HPSham, EYYu, MFGulen, GBhinder, MStahl, JMChan, et al. SIGIRR, a negative regulator of TLR/IL-1R signalling promotes Microbiota dependent resistance to colonization by enteric bacterial pathogens. PLoS Pathog 2013;9:e1003539.
  • MHMaillard, HBega, HHUhlig, NBarnich, TGrandjean, MChamaillard, et al. Toll-interacting protein modulates colitis susceptibility in mice. Inflamm Bowel Dis 2014;20:660–70.
  • TBGeijtenbeek, SIGringhuis. Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 2009;9:465–79.
  • PGWhitney, EBar, FOsorio, NCRogers, BUSchraml, SDeddouche, et al. Syk signaling in dendritic cells orchestrates innate resistance to systemic fungal infection. PLoS Pathog 2014;10:e1004276.
  • IDIliev, VAFunari, KDTaylor, QNguyen, CNReyes, SPStrom, et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 2012;336:1314–17.
  • GChen, MHShaw, YGKim, GNunez. NOD-like receptors: role in innate immunity and inflammatory disease. Annu Rev Pathol 2009;4:365–98.
  • MHedl, JLi, JHCho, CAbraham. Chronic stimulation of Nod2 mediates tolerance to bacterial products. Proc Natl Acad Sci USA 2007;104:19440–5.
  • BJKullberg, GFerwerda, DJde Jong, JPDrenth, LAJoosten, JWVan der Meer, et al. Crohn’s disease patients homozygous for the 3020insC NOD2 mutation have a defective NOD2/TLR4 cross-tolerance to intestinal stimuli. Immunology 2008;123:600–5.
  • SZheng, CAbraham. NF-kappaB1 inhibits NOD2-induced cytokine secretion through ATF3-dependent mechanisms. Mol Cell Biol 2013;33:4857–71.
  • RCooney, JBaker, OBrain, BDanis, TPichulik, PAllan, et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 2010;16:90–7.
  • MTSorbara, LKEllison, MRamjeet, LHTravassos, NLJones, SEGirardin, et al. The protein ATG16L1 suppresses inflammatory cytokines induced by the intracellular sensors Nod1 and Nod2 in an autophagy-independent manner. Immunity 2013;39:858–73.
  • LFranchi, TEigenbrod, GNunez. Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J Immunol 2009;183:792–6.
  • CBauer, PDuewell, CMayer, HALehr, KAFitzgerald, MDauer, et al. Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut 2010;59:1192–9.
  • LYHao, XLiu, LFranchi. Inflammasomes in inflammatory bowel disease pathogenesis. Curr Opin Gastroenterol 2013;29:363–9.
  • NEastaff-Leung, NMabarrack, ABarbour, ACummins, SBarry. Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. J Clin Immunol 2010;30:80–9.
  • EElinav, TStrowig, ALKau, JHenao-Mejia, CAThaiss, CJBooth, et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 2011;145:745–57.
  • MWlodarska, CAThaiss, RNowarski, JHenao-Mejia, JPZhang, EMBrown, et al. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 2014;156:1045–59.
  • AMMowat. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol 2003;3:331–41.
  • IDIliev, GMatteoli, MRescigno. The yin and yang of intestinal epithelial cells in controlling dendritic cell function. J Exp Med 2007;204:2253–7.
  • JMDavies, JMacSharry, FShanahan. Differential regulation of Toll-like receptor signalling in spleen and Peyer’s patch dendritic cells. Immunology 2010;131:438–48.
  • STakenaka, ESafroneeva, ZXing, JGauldie. Dendritic cells derived from murine colonic mucosa have unique functional and phenotypic characteristics. J Immunol 2007;178:7984–93.
  • IMonteleone, AMPlatt, EJaensson, WWAgace, AMMowat. IL-10-dependent partial refractoriness to Toll-like receptor stimulation modulates gut mucosal dendritic cell function. Eur J Immunol 2008;38:1533–47.
  • MRimoldi, MChieppa, VSalucci, FAvogadri, ASonzogni, GMSampietro, et al. Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat Immunol 2005;6:507–14.
  • ALHart, HOAl-Hassi, RJRigby, SJBell, AVEmmanuel, SCKnight, et al. Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology 2005;129:50–65.
  • JEQualls, HTuna, AMKaplan, DACohen. Suppression of experimental colitis in mice by CD11c+ dendritic cells. Inflamm Bowel Dis 2009;15:236–47.
  • JEQualls, AMKaplan, Nvan Rooijen, DACohen. Suppression of experimental colitis by intestinal mononuclear phagocytes. J Leukoc Biol 2006;80:802–15.
  • MATravis, BReizis, ACMelton, EMasteller, QTang, JMProctor, et al. Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature 2007;449:361–5.
  • JErmann, TStaton, JNGlickman, Rde Waal Malefyt, LHGlimcher. Nod/Ripk2 signaling in dendritic cells activates IL-17A-secreting innate lymphoid cells and drives colitis in T-bet-/-.Rag2-/- (TRUC) mice. Proc Natl Acad Sci USA 2014;111:E2559–66.
  • YNaito, TTakagi, TYoshikawa. Neutrophil-dependent oxidative stress in ulcerative colitis. J Clin Biochem Nutr 2007;41:18–26.
  • HHanai, KTakeuchi, TIida, NKashiwagi, ARSaniabadi, IMatsushita, et al. Relationship between fecal calprotectin, intestinal inflammation, and peripheral blood neutrophils in patients with active ulcerative colitis. Dig Dis Sci 2004;49:1438–43.
  • YMorohoshi, KMatsuoka, HChinen, NKamada, TSato, THisamatsu, et al. Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis. J Gastroenterol 2006;41:318–24.
  • RSomasundaram, VJNuij, CJvan der Woude, EJKuipers, MPPeppelenbosch, GMFuhler. Peripheral neutrophil functions and cell signalling in Crohn`s disease. PLoS One 2013;8:e84521.
  • LJHall, EFaivre, AQuinlan, FShanahan, KNally, SMelgar. Induction and activation of adaptive immune populations during acute and chronic phases of a murine model of experimental colitis. Dig Dis Sci 2011;56:79–89.
  • MNatsui, KKawasaki, HTakizawa, SIHayashi, YMatsuda, KSugimura, et al. Selective depletion of neutrophils by a monoclonal antibody, RP-3, suppresses dextran sulphate sodium-induced colitis in rats. J Gastroenterol Hepatol 1997;12:801–8.
  • TTaniguchi, HTsukada, HNakamura, MKodama, KFukuda, TSaito, et al. Effects of the anti-ICAM-1 monoclonal antibody on dextran sodium sulphate-induced colitis in rats. J Gastroenterol Hepatol 1998;13:945–9.
  • AGeremia, CVArancibia-Carcamo, MPFleming, NRust, BSingh, NJMortensen, et al. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med 2011;208:1127–33.
  • TCupedo, NKCrellin, NPapazian, EJRombouts, KWeijer, JLGrogan, et al. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat Immunol 2009;10:66–74.
  • DJCua, CMTato. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 2010;10:479–89.
  • TTakayama, NKamada, HChinen, SOkamoto, MTKitazume, JChang, et al. Imbalance of NKp44(+)NKp46(-) and NKp44(-)NKp46(+) natural killer cells in the intestinal mucosa of patients with Crohn’s disease. Gastroenterology 2010;139:882–92. 92 e1-3.
  • HTakatori, YKanno, WTWatford, CMTato, GWeiss, IIIvanov, et al. Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med 2009;206:35–41.
  • SBuonocore, PPAhern, HHUhlig, IIIvanov, DRLittman, KJMaloy, et al. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 2010;464:1371–5.
  • HHUhlig, BSMcKenzie, SHue, CThompson, BJoyce-Shaikh, RStepankova, et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 2006;25:309–18.
  • WJSandborn, BGFeagan, RNFedorak, EScherl, MRFleisher, SKatz, Ustekinumab Crohn’s Disease Study G. A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn’s disease. Gastroenterology 2008;135:1130–41.
  • NKCrellin, STrifari, CDKaplan, NSatoh-Takayama, JPDi Santo, HSpits. Regulation of cytokine secretion in human CD127(+) LTi-like innate lymphoid cells by Toll-like receptor 2. Immunity 2010;33:752–64.
  • GFSonnenberg, LAFouser, DArtis. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol 2011;12:383–90.
  • GPickert, CNeufert, MLeppkes, YZheng, NWittkopf, MWarntjen, et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med 2009;206:1465–72.
  • YZheng, PAValdez, DMDanilenko, YHu, SMSa, QGong, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 2008;14:282–9.
  • CLZindl, JFLai, YKLee, CLMaynard, SNHarbour, WOuyang, et al. IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis. Proc Natl Acad Sci USA 2013;110:12768–73.
  • LAZenewicz, GDYancopoulos, DMValenzuela, AJMurphy, SStevens, RAFlavell. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 2008;29:947–57.
  • MAKinnebrew, CGBuffie, GEDiehl, LAZenewicz, ILeiner, TMHohl, et al. Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 2012;36:276–87.
  • GFSonnenberg, LAMonticelli, TAlenghat, TCFung, NAHutnick, JKunisawa, et al. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 2012;336:1321–5.
  • MRHepworth, LAMonticelli, TCFung, CGZiegler, SGrunberg, RSinha, et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature 2013;498:113–17.
  • SFujino, AAndoh, SBamba, AOgawa, KHata, YAraki, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 2003;52:65–70.
  • VHoltta, PKlemetti, TSipponen, MWesterholm-Ormio, GKociubinski, HSalo, et al. IL-23/IL-17 immunity as a hallmark of Crohn’s disease. Inflamm Bowel Dis 2008;14:1175–84.
  • AOgawa, AAndoh, YAraki, TBamba, YFujiyama. Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced colitis in mice. Clin Immunol 2004;110:55–62.
  • XOYang, SHChang, HPark, RNurieva, BShah, LAcero, et al. Regulation of inflammatory responses by IL-17F. J Exp Med 2008;205:1063–75.
  • WO’ConnorJr, MKamanaka, CJBooth, TTown, SNakae, YIwakura, et al. A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol 2009;10:603–9.
  • WHueber, BESands, SLewitzky, MVandemeulebroecke, WReinisch, PDHiggins, Secukinumab in Crohn’s Disease Study G. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 2012;61:1693–700.
  • SRTargan, BGFeagan, SVermeire, RPanaccione, GYMelmed, CBlosch, et al. Mo2083 a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of AMG 827 in subjects with moderate to severe crohn’s disease. Gastroenterology 2012;143:e26.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.