Current Infectious Disease Reports

, Volume 14, Issue 1, pp 15–23 | Cite as

The Role of Innate Immunity in the Host Defense Against Intestinal Bacterial Pathogens

Intra-abdominal Infections, Hepatitis, and Gastroenteritis (DA Bobak, Section Editor)
First Online:

Abstract

Eradication of infectious disease is our global health challenge. After encountering intestinal infection with a bacterial pathogen, the host defense program is initiated by local antigen-presenting cells (APCs) that eliminate invading pathogens by phagocytosis and establish localized inflammation by secreting cytokines and chemokines. These pathogen-experienced APCs migrate to the mesenteric lymph nodes, where host immune responses are precisely orchestrated. Initiation and regulation of this defense program appear to be largely dependent on innate immunity which is antigen non-specific and provides a rapid defense against broader targets. On the other hand, many bacterial enteropathogens have evoked abilities to modify the host defense program to their advantage. Therefore, better understanding of the host-pathogen interactions is essential to establish effective eradication strategies for enteric infectious diseases. In this review, we will discuss the current understanding of innate immune regulation of the host defense mechanisms against intestinal infection by bacterial pathogens.

Keywords

Innate immunity Bacterial pathogens Host defense Macrophages Enteropathogen Gram-negative Toll-like receptors Nod-like receptors Mucosal defense Protective immunity Antimicrobial peptide Secretory IgA Commensals 
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Notes

Acknowledgments

The contents of this review was supported by National Institute of Allergy and Infectious Diseases (R56 AI095255) and Senior Research Award from Crohn’s Colitis Foundation of America for M.F.

Disclosure

No potential conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Helms M, Vastrup P, Gerner-Smidt P, Molbak K. Short and long term mortality associated with foodborne bacterial gastrointestinal infections: registry based study. BMJ. 2003;326:357.PubMedCrossRefGoogle Scholar
  2. 2.
    Yee EL, Palacio H, Atmar RL, Shah U, Kilborn C, Faul M, et al. Widespread outbreak of norovirus gastroenteritis among evacuees of Hurricane Katrina residing in a large “megashelter” in Houston, Texas: lessons learned for prevention. Clin Infect Dis. 2007;44:1032–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Walton DA, Ivers LC. Responding to cholera in post-earthquake Haiti. N Engl J Med. 2011;364:3–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Zarocostas J. Experts urge vaccination to try to control cholera outbreak in Haiti. BMJ. 2011;342:d23.PubMedCrossRefGoogle Scholar
  5. 5.
    Niedergang F, Didierlaurent A, Kraehenbuhl JP, Sirard JC. Dendritic cells: the host Achille’s heel for mucosal pathogens? Trends Microbiol. 2004;12:79–88.PubMedCrossRefGoogle Scholar
  6. 6.
    Miao EA, Miller SI. Bacteriophages in the evolution of pathogen-host interactions. Proc Natl Acad Sci U S A. 1999;96:9452–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Brodsky IE, Medzhitov R. Reduced secretion of YopJ by Yersinia limits in vivo cell death but enhances bacterial virulence. PLoS Pathog. 2008;4:e1000067.PubMedCrossRefGoogle Scholar
  8. 8.
    Arnold R, Jehl A, Rattei T. Targeting effectors: the molecular recognition of Type III secreted proteins. Microbes Infect. 2010;12:346–58.PubMedCrossRefGoogle Scholar
  9. 9.
    Tyrer P, Foxwell AR, Cripps AW, Apicella MA, Kyd JM. Microbial pattern recognition receptors mediate M-cell uptake of a gram-negative bacterium. Infect Immun. 2006;74:625–31.PubMedCrossRefGoogle Scholar
  10. 10.
    Rydstrom A, Wick MJ. Monocyte recruitment, activation, and function in the gut-associated lymphoid tissue during oral Salmonella infection. J Immunol. 2007;178:5789–801.PubMedGoogle Scholar
  11. 11.
    Salazar-Gonzalez RM, Niess JH, Zammit DJ, Ravindran R, Srinivasan A, Maxwell JR, et al. CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer’s patches. Immunity. 2006;24:623–32.PubMedCrossRefGoogle Scholar
  12. 12.
    Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol. 2001;2:361–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Niess JH, Brand S, Gu X, Landsman L, Jung S, McCormick BA, et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science. 2005;307:254–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Chieppa M, Rescigno M, Huang AY, Germain RN. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J Exp Med. 2006;203:2841–52.PubMedCrossRefGoogle Scholar
  15. 15.
    Vallon-Eberhard A, Landsman L, Yogev N, Verrier B, Jung S. Transepithelial pathogen uptake into the small intestinal lamina propria. J Immunol. 2006;176:2465–9.PubMedGoogle Scholar
  16. 16.
    Uematsu S, Jang MH, Chevrier N, Guo Z, Kumagai Y, Yamamoto M, et al. Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells. Nat Immunol. 2006;7:868–74.PubMedCrossRefGoogle Scholar
  17. 17.
    Macpherson AJ, Uhr T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science. 2004;303:1662–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Westphal S, Lugering A, von Wedel J, von Eiff C, Maaser C, Spahn T, et al. Resistance of chemokine receptor 6-deficient mice to Yersinia enterocolitica infection: evidence of defective M-cell formation in vivo. Am J Pathol. 2008;172:671–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Voedisch S, Koenecke C, David S, Herbrand H, Forster R, Rhen M, et al. Mesenteric lymph nodes confine dendritic cell-mediated dissemination of Salmonella enterica serovar Typhimurium and limit systemic disease in mice. Infect Immun. 2009;77:3170–80.PubMedCrossRefGoogle Scholar
  20. 20.
    Fukata M, Michelsen KS, Eri R, Thomas LS, Hu B, Lukasek K, 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.PubMedCrossRefGoogle Scholar
  21. 21.
    Coburn B, Grassl GA, Finlay BB. Salmonella, the host and disease: a brief review. Immunol Cell Biol. 2007;85:112–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Hapfelmeier S, Hardt WD. A mouse model for S. typhimurium-induced enterocolitis. Trends Microbiol. 2005;13:497–503.PubMedCrossRefGoogle Scholar
  23. 23.
    Heesemann J, Gaede K, Autenrieth IB. Experimental Yersinia enterocolitica infection in rodents: a model for human yersiniosis. APMIS. 1993;101:417–29.PubMedCrossRefGoogle Scholar
  24. 24.
    Mundy R, MacDonald TT, Dougan G, Frankel G, Wiles S. Citrobacter rodentium of mice and man. Cell Microbiol. 2005;7:1697–706.PubMedCrossRefGoogle Scholar
  25. 25.
    Borenshtein D, McBee ME, Schauer DB. Utility of the Citrobacter rodentium infection model in laboratory mice. Curr Opin Gastroenterol. 2008;24:32–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Fox JG, Ge Z, Whary MT, Erdman SE, Horwitz BH. Helicobacter hepaticus infection in mice: models for understanding lower bowel inflammation and cancer. Mucosal Immunol. 2011;4:22–30.PubMedCrossRefGoogle Scholar
  27. 27.
    Maloy KJ, Salaun L, Cahill R, Dougan G, Saunders NJ, Powrie F. CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med. 2003;197:111–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Melmed G, Thomas LS, Lee N, Tesfay SY, Lukasek K, Michelsen KS, et al. Human intestinal epithelial cells are broadly unresponsive to Toll-like receptor 2-dependent bacterial ligands: implications for host-microbial interactions in the gut. J Immunol. 2003;170:1406–15.PubMedGoogle Scholar
  29. 29.
    Otte JM, Cario E, Podolsky DK. Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells. Gastroenterology. 2004;126:1054–70.PubMedCrossRefGoogle Scholar
  30. 30.
    Smythies LE, Sellers M, Clements RH, Mosteller-Barnum M, Meng G, Benjamin WH, et al. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest. 2005;115:66–75.PubMedGoogle Scholar
  31. 31.
    Weiss DS, Raupach B, Takeda K, Akira S, Zychlinsky A. Toll-like receptors are temporally involved in host defense. J Immunol. 2004;172:4463–9.PubMedGoogle Scholar
  32. 32.
    Vazquez-Torres A, Vallance BA, Bergman MA, Finlay BB, Cookson BT, Jones-Carson J, et al. Toll-like receptor 4 dependence of innate and adaptive immunity to Salmonella: importance of the Kupffer cell network. J Immunol. 2004;172:6202–8.PubMedGoogle Scholar
  33. 33.
    Sing A, Tvardovskaia N, Rost D, Kirschning CJ, Wagner H, Heesemann J. Contribution of toll-like receptors 2 and 4 in an oral Yersinia enterocolitica mouse infection model. Int J Med Microbiol. 2003;293:341–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Franchi L, Amer A, Body-Malapel M, Kanneganti TD, Ozoren N, Jagirdar R, et al. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages. Nat Immunol. 2006;7:576–82.PubMedCrossRefGoogle Scholar
  35. 35.
    Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature. 2004;430:213–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Miao EA, Alpuche-Aranda CM, Dors M, Clark AE, Bader MW, Miller SI, et al. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf. Nat Immunol. 2006;7:569–75.PubMedCrossRefGoogle Scholar
  37. 37.
    Lara-Tejero M, Sutterwala FS, Ogura Y, Grant EP, Bertin J, Coyle AJ, et al. Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis. J Exp Med. 2006;203:1407–12.PubMedCrossRefGoogle Scholar
  38. 38.
    Raupach B, Peuschel SK, Monack DM, Zychlinsky A. Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection. Infect Immun. 2006;74:4922–6.PubMedCrossRefGoogle Scholar
  39. 39.
    •• Arpaia N, Godec J, Lau L, Sivick KE, McLaughlin LM, Jones MB, et al. TLR signaling is required for Salmonella typhimurium virulence. Cell. 2011;144:675–88. This article nicely shows how TLR signaling forms host-pathogen interactions during S. typhimurium infection. Certain TLR signaling contributes to host effector immunity, but other TLR signaling may be used as virulence effector of the pathogen.PubMedCrossRefGoogle Scholar
  40. 40.
    Khan MA, Ma C, Knodler LA, Valdez Y, Rosenberger CM, Deng W, et al. Toll-like receptor 4 contributes to colitis development but not to host defense during Citrobacter rodentium infection in mice. Infect Immun. 2006;74:2522–36.PubMedCrossRefGoogle Scholar
  41. 41.
    • Asquith MJ, Boulard O, Powrie F, Maloy KJ. Pathogenic and protective roles of MyD88 in leukocytes and epithelial cells in mouse models of inflammatory bowel disease. Gastroenterology. 2010;139:519–29. This study shows distinct contributions of TLR signaling by cell type in induction of intestinal inflammation. MyD88 signaling in myeloid cells is responsible for induction of innate inflammation in the intestine.PubMedCrossRefGoogle Scholar
  42. 42.
    Lamm ME. Interaction of antigens and antibodies at mucosal surfaces. Annu Rev Microbiol. 1997;51:311–40.PubMedCrossRefGoogle Scholar
  43. 43.
    Shimada S, Kawaguchi-Miyashita M, Kushiro A, Sato T, Nanno M, Sako T, et al. Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA. J Immunol. 1999;163:5367–73.PubMedGoogle Scholar
  44. 44.
    Ouellette AJ. Paneth cell alpha-defensins in enteric innate immunity. Cell Mol Life Sci. 2011;68:2215–29.PubMedCrossRefGoogle Scholar
  45. 45.
    Shroff KE, Meslin K, Cebra JJ. Commensal enteric bacteria engender a self-limiting humoral mucosal immune response while permanently colonizing the gut. Infect Immun. 1995;63:3904–13.PubMedGoogle Scholar
  46. 46.
    Brandtzaeg P, Johansen FE. Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunol Rev. 2005;206:32–63.PubMedCrossRefGoogle Scholar
  47. 47.
    Sundstrom P, Lundin SB, Nilsson LA, Quiding-Jarbrink M. Human IgA-secreting cells induced by intestinal, but not systemic, immunization respond to CCL25 (TECK) and CCL28 (MEC). Eur J Immunol. 2008;38:3327–38.PubMedCrossRefGoogle Scholar
  48. 48.
    Hahne M, Kataoka T, Schroter M, Hofmann K, Irmler M, Bodmer JL, et al. APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J Exp Med. 1998;188:1185–90.PubMedCrossRefGoogle Scholar
  49. 49.
    Mackay F, Schneider P, Rennert P, Browning J. BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003;21:231–64.PubMedCrossRefGoogle Scholar
  50. 50.
    Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P, et al. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol. 2002;3:822–9.PubMedCrossRefGoogle Scholar
  51. 51.
    He B, Xu W, Santini PA, Polydorides AD, Chiu A, Estrella J, et al. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity. 2007;26:812–26.PubMedCrossRefGoogle Scholar
  52. 52.
    Bouvet JP, Dighiero G. From natural polyreactive autoantibodies to a la carte monoreactive antibodies to infectious agents: is it a small world after all? Infect Immun. 1998;66:1–4.PubMedGoogle Scholar
  53. 53.
    Notkins AL. Polyreactivity of antibody molecules. Trends Immunol. 2004;25:174–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Shang L, Fukata M, Thirunarayanan N, Martin AP, Arnaboldi P, Maussang D, et al. Toll-like receptor signaling in small intestinal epithelium promotes B-cell recruitment and IgA production in lamina propria. Gastroenterology. 2008;135:529–38.PubMedCrossRefGoogle Scholar
  55. 55.
    Bruno ME, Rogier EW, Frantz AL, Stefka AT, Thompson SN, Kaetzel CS. Regulation of the polymeric immunoglobulin receptor in intestinal epithelial cells by Enterobacteriaceae: implications for mucosal homeostasis. Immunol Invest. 2010;39:356–82.PubMedCrossRefGoogle Scholar
  56. 56.
    Schneeman TA, Bruno ME, Schjerven H, Johansen FE, Chady L, Kaetzel CS. Regulation of the polymeric Ig receptor by signaling through TLRs 3 and 4: linking innate and adaptive immune responses. J Immunol. 2005;175:376–84.PubMedGoogle Scholar
  57. 57.
    Wijburg OL, Uren TK, Simpfendorfer K, Johansen FE, Brandtzaeg P, Strugnell RA. Innate secretory antibodies protect against natural Salmonella typhimurium infection. J Exp Med. 2006;203:21–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol. 2003;3:710–20.PubMedCrossRefGoogle Scholar
  59. 59.
    Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, et al. Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science. 1999;286:113–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature. 2003;422:522–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Vaishnava S, Behrendt CL, Ismail AS, Eckmann L, Hooper LV. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc Natl Acad Sci U S A. 2008;105:20858–63.PubMedCrossRefGoogle Scholar
  62. 62.
    Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 2005;307:731–4.PubMedCrossRefGoogle Scholar
  63. 63.
    Lee J, Mo JH, Katakura K, Alkalay I, Rucker AN, Liu YT, et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol. 2006;8:1327–36.PubMedCrossRefGoogle Scholar
  64. 64.
    Hisamatsu T, Suzuki M, Reinecker HC, Nadeau WJ, McCormick BA, Podolsky DK. CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells. Gastroenterology. 2003;124:993–1000.PubMedCrossRefGoogle Scholar
  65. 65.
    Petnicki-Ocwieja T, Hrncir T, Liu YJ, Biswas A, Hudcovic T, Tlaskalova-Hogenova H, et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci U S A. 2009;106:15813–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Uehara A, Fujimoto Y, Fukase K, Takada H. Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol. 2007;44:3100–11.PubMedCrossRefGoogle Scholar
  67. 67.
    Vora P, Youdim A, Thomas LS, Fukata M, Tesfay SY, Lukasek K, et al. Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J Immunol. 2004;173:5398–405.PubMedGoogle Scholar
  68. 68.
    Blander JM, Medzhitov R. Regulation of phagosome maturation by signals from toll-like receptors. Science. 2004;304:1014–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Blander JM, Medzhitov R. Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature. 2006;440:808–12.PubMedCrossRefGoogle Scholar
  70. 70.
    Kong L, Sun L, Zhang H, Liu Q, Liu Y, Qin L, et al. An essential role for RIG-I in toll-like receptor-stimulated phagocytosis. Cell Host Microbe. 2009;6:150–61.PubMedCrossRefGoogle Scholar
  71. 71.
    Rosenberger CM, Finlay BB. Phagocyte sabotage: disruption of macrophage signalling by bacterial pathogens. Nat Rev Mol Cell Biol. 2003;4:385–96.PubMedCrossRefGoogle Scholar
  72. 72.
    Wong CE, Sad S, Coombes BK. Salmonella enterica serovar typhimurium exploits Toll-like receptor signaling during the host-pathogen interaction. Infect Immun. 2009;77:4750–60.PubMedCrossRefGoogle Scholar
  73. 73.
    Di Santo JP. Functionally distinct NK-cell subsets: developmental origins and biological implications. Eur J Immunol. 2008;38:2948–51.PubMedCrossRefGoogle Scholar
  74. 74.
    Ashkar AA, Reid S, Verdu EF, Zhang K, Coombes BK. Interleukin-15 and NK1.1+ cells provide innate protection against acute Salmonella enterica serovar Typhimurium infection in the gut and in systemic tissues. Infect Immun. 2009;77:214–22.PubMedCrossRefGoogle Scholar
  75. 75.
    Harrington L, Srikanth CV, Antony R, Shi HN, Cherayil BJ. A role for natural killer cells in intestinal inflammation caused by infection with Salmonella enterica serovar Typhimurium. FEMS Immunol Med Microbiol. 2007;51:372–80.PubMedCrossRefGoogle Scholar
  76. 76.
    Reynders A, Yessaad N, Vu Manh TP, Dalod M, Fenis A, Aubry C, et al. Identity, regulation and in vivo function of gut NKp46+RORgammat+ and NKp46+RORgammat- lymphoid cells. EMBO J. 2011;30:2934–47.PubMedCrossRefGoogle Scholar
  77. 77.
    Sonnenberg GF, Monticelli LA, Elloso MM, Fouser LA, Artis D. CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity. 2011;34:122–34.PubMedCrossRefGoogle Scholar
  78. 78.
    Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature. 2009;457:722–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Mayuzumi H, Inagaki-Ohara K, Uyttenhove C, Okamoto Y, Matsuzaki G. Interleukin-17A is required to suppress invasion of Salmonella enterica serovar Typhimurium to enteric mucosa. Immunology. 2010;131:377–85.PubMedCrossRefGoogle Scholar
  80. 80.
    Raffatellu M, Santos RL, Verhoeven DE, George MD, Wilson RP, Winter SE, et al. Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med. 2008;14:421–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, Gong Q, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med. 2008;14:282–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Graham AC, Carr KD, Sieve AN, Indramohan M, Break TJ, Berg RE. IL-22 production is regulated by IL-23 during Listeria monocytogenes infection but is not required for bacterial clearance or tissue protection. PLoS One. 2011;6:e17171.PubMedCrossRefGoogle Scholar
  83. 83.
    Lebeis SL, Powell KR, Merlin D, Sherman MA, Kalman D. Interleukin-1 receptor signaling protects mice from lethal intestinal damage caused by the attaching and effacing pathogen Citrobacter rodentium. Infect Immun. 2009;77:604–14.PubMedCrossRefGoogle Scholar
  84. 84.
    Guo B, Cheng G. Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK. J Biol Chem. 2007;282:11817–26.PubMedCrossRefGoogle Scholar
  85. 85.
    Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003;301:640–3.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Division of Gastroenterology, Department of MedicineUniversity of Miami Miller School of MedicineMiamiUSA

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