Commensal DNA Limits Regulatory T Cell Conversion and Is a Natural Adjuvant of Intestinal Immune Responses

Immunity

Volumn 29, Issue 4, 2008, Pages 637-649

  Hall, Jason A ^a,b   Bouladoux, Nicolas ^a   Sun, Cheng Ming ^a   Wohlfert, Elizabeth A ^a   Blank, Rebecca B ^a   Zhu, Qing ^c   Grigg, Michael E ^a   Berzofsky, Jay A ^c   Belkaid, Yasmine ^a  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

CELLIMMUNO

Indexed keywords

AMPICILLIN; ANTIBIOTIC AGENT; CD4 ANTIGEN; DNA; GAMMA INTERFERON; INTERLEUKIN 17; METRONIDAZOLE; NEOMYCIN; TOLL LIKE RECEPTOR 9; TRANSCRIPTION FACTOR FOXP3; VANCOMYCIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENDRITIC CELL; EFFECTOR CELL; HOMEOSTASIS; IMMUNOPATHOLOGY; IMMUNOREACTIVITY; IN VITRO STUDY; INTESTINE FLORA; LAMINA PROPRIA; LYMPHOCYTE COUNT; MALE; MICROSPORIDIOSIS; MOUSE; MOUTH INFECTION; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; VACCINATION;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; ANTI-BACTERIAL AGENTS; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; DENDRITIC CELLS; DNA, BACTERIAL; IMMUNITY, MUCOSAL; INTERFERON-GAMMA; INTERLEUKIN-17; INTESTINAL MUCOSA; INTESTINES; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MUCOUS MEMBRANE; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; T-LYMPHOCYTES, REGULATORY; TOLL-LIKE RECEPTOR 9;

EID: 53349164200     PISSN: 10747613     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.immuni.2008.08.009     Document Type: Article

References (71)

1. Backhed F., Ley R.E., Sonnenburg J.L., Peterson D.A., and Gordon J.I. Host-bacterial mutualism in the human intestine. Science 307 (2005) 1915-1920
2. Barnich N., Boudeau J., Claret L., and Darfeuille-Michaud A. Regulatory and functional co-operation of flagella and type 1 pili in adhesive and invasive abilities of AIEC strain LF82 isolated from a patient with Crohn's disease. Mol. Microbiol. 48 (2003) 781-794
3. Bashir M.E., Louie S., Shi H.N., and Nagler-Anderson C. Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy. J. Immunol. 172 (2004) 6978-6987
4. Benson M.J., Pino-Lagos K., Rosemblatt M., and Noelle R.J. All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J. Exp. Med. 204 (2007) 1765-1774
5. Bettelli E., Carrier Y., Gao W., Korn T., Strom T.B., Oukka M., Weiner H.L., and Kuchroo V.K. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441 (2006) 235-238
6. Bouladoux N., Biligui S., and Desportes-Livage I. A new monoclonal antibody enzyme-linked immunosorbent assay to measure in vitro multiplication of the microsporidium Encephalitozoon intestinalis. J. Microbiol. Methods 53 (2003) 377-385
7. Brenchley J.M., Price D.A., Schacker T.W., Asher T.E., Silvestri G., Rao S., Kazzaz Z., Bornstein E., Lambotte O., Altmann D., et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat. Med. 12 (2006) 1365-1371
8. Bucci C., Parton R.G., Mather I.H., Stunnenberg H., Simons K., Hoflack B., and Zerial M. The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell 70 (1992) 715-728
9. Caramalho I., Lopes-Carvalho T., Ostler D., Zelenay S., Haury M., and Demengeot J. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J. Exp. Med. 197 (2003) 403-411
10. Chieppa M., Rescigno M., Huang A.Y., and Germain R.N. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J. Exp. Med. 203 (2006) 2841-2852
11. Chong C., Friberg M., and Clements J.D. LT(R192G), a non-toxic mutant of the heat-labile enterotoxin of Escherichia coli, elicits enhanced humoral and cellular immune responses associated with protection against lethal oral challenge with Salmonella spp. Vaccine 16 (1998) 732-740
12. Coombes J.L., Siddiqui K.R., Arancibia-Carcamo C.V., Hall J., Sun C.M., Belkaid Y., and Powrie F. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J. Exp. Med. 204 (2007) 1757-1764
13. Crellin N.K., Garcia R.V., Hadisfar O., Allan S.E., Steiner T.S., and Levings M.K. Human CD4+ T cells express TLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP3 in CD4+CD25+ T regulatory cells. J. Immunol. 175 (2005) 8051-8059
14. Dalpke A., Frank J., Peter M., and Heeg K. Activation of toll-like receptor 9 by DNA from different bacterial species. Infect. Immun. 74 (2006) 940-946
15. Darfeuille-Michaud A., Boudeau J., Bulois P., Neut C., Glasser A.L., Barnich N., Bringer M.A., Swidsinski A., Beaugerie L., and Colombel J.F. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 127 (2004) 412-421
16. Denning T.L., Wang Y.C., Patel S.R., Williams I.R., and Pulendran B. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat. Immunol. 8 (2007) 1086-1094
17. Didier E.S. Microsporidiosis: An emerging and opportunistic infection in humans and animals. Acta Trop. 94 (2005) 61-76
18. Ewaschuk J.B., Backer J.L., Churchill T.A., Obermeier F., Krause D.O., and Madsen K.L. Surface expression of Toll-like receptor 9 is upregulated on intestinal epithelial cells in response to pathogenic bacterial DNA. Infect. Immun. 75 (2007) 2572-2579
19. Fukata M., Michelsen K.S., Eri R., Thomas L.S., Hu B., Lukasek K., Nast C.C., Lechago J., Xu R., Naiki Y., 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. 288 (2005) G1055-G1065
20. Heimesaat M.M., Bereswill S., Fischer A., Fuchs D., Struck D., Niebergall J., Jahn H.K., Dunay I.R., Moter A., Gescher D.M., et al. Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii. J. Immunol. 177 (2006) 8785-8795
21. Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H., Matsumoto M., Hoshino K., Wagner H., Takeda K., and Akira S. A Toll-like receptor recognizes bacterial DNA. Nature 408 (2000) 740-745
22. Izcue A., Coombes J.L., and Powrie F. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol. Rev. 212 (2006) 256-271
23. Johansson-Lindbom B., Svensson M., Pabst O., Palmqvist C., Marquez G., Forster R., and Agace W.W. Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing. J. Exp. Med. 202 (2005) 1063-1073
24. Johansson-Lindbom B., Svensson M., Wurbel M.A., Malissen B., Marquez G., and Agace W. Selective generation of gut tropic T cells in gut-associated lymphoid tissue (GALT): Requirement for GALT dendritic cells and adjuvant. J. Exp. Med. 198 (2003) 963-969
25. Katakura K., Lee J., Rachmilewitz D., Li G., Eckmann L., and Raz E. Toll-like receptor 9-induced type I IFN protects mice from experimental colitis. J. Clin. Invest. 115 (2005) 695-702
26. Khan I.A., and Moretto M. Role of gamma interferon in cellular immune response against murine Encephalitozoon cuniculi infection. Infect. Immun. 67 (1999) 1887-1893
27. Korn T., Bettelli E., Gao W., Awasthi A., Jager A., Strom T.B., Oukka M., and Kuchroo V.K. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448 (2007) 484-487
28. Larosa D.F., Gelman A.E., Rahman A.H., Zhang J., Turka L.A., and Walsh P.T. CpG DNA inhibits CD4+CD25+ Treg suppression through direct MyD88-dependent costimulation of effector CD4+ T cells. Immunol. Lett. 108 (2007) 183-188
29. Lee J., Mo J.H., Katakura K., Alkalay I., Rucker A.N., Liu Y.T., Lee H.K., Shen C., Cojocaru G., Shenouda S., et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat. Cell Biol. 8 (2006) 1327-1336
30. Liu H., Komai-Koma M., Xu D., and Liew F.Y. Toll-like receptor 2 signaling modulates the functions of CD4+ CD25+ regulatory T cells. Proc. Natl. Acad. Sci. USA 103 (2006) 7048-7053
31. Lotz M., Gutle D., Walther S., Menard S., Bogdan C., and Hornef M.W. Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells. J. Exp. Med. 203 (2006) 973-984
32. Lund J., Sato A., Akira S., Medzhitov R., and Iwasaki A. Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J. Exp. Med. 198 (2003) 513-520
33. Lutz M.B., Kukutsch N., Ogilvie A.L., Rossner S., Koch F., Romani N., and Schuler G. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J. Immunol. Methods 223 (1999) 77-92
34. Martin H.M., Campbell B.J., Hart C.A., Mpofu C., Nayar M., Singh R., Englyst H., Williams H.F., and Rhodes J.M. Enhanced Escherichia coli adherence and invasion in Crohn's disease and colon cancer. Gastroenterology 127 (2004) 80-93
35. Masseret E., Boudeau J., Colombel J.F., Neut C., Desreumaux P., Joly B., Cortot A., and Darfeuille-Michaud A. Genetically related Escherichia coli strains associated with Crohn's disease. Gut 48 (2001) 320-325
36. Medzhitov R., Preston-Hurlburt P., and Janeway Jr. C.A. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388 (1997) 394-397
37. Min B., Thornton A., Caucheteux S.M., Younes S.A., Oh K., Hu-Li J., and Paul W.E. Gut flora antigens are not important in the maintenance of regulatory T cell heterogeneity and homeostasis. Eur. J. Immunol. 37 (2007) 1916-1923
38. Minns L.A., Menard L.C., Foureau D.M., Darche S., Ronet C., Mielcarz D.W., Buzoni-Gatel D., and Kasper L.H. TLR9 is required for the gut-associated lymphoid tissue response following oral infection of Toxoplasma gondii. J. Immunol. 176 (2006) 7589-7597
39. Mora J.R., Iwata M., Eksteen B., Song S.Y., Junt T., Senman B., Otipoby K.L., Yokota A., Takeuchi H., Ricciardi-Castagnoli P., et al. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314 (2006) 1157-1160
40. Moretto M., Weiss L.M., and Khan I.A. Induction of a rapid and strong antigen-specific intraepithelial lymphocyte response during oral Encephalitozoon cuniculi infection. J. Immunol. 172 (2004) 4402-4409
41. Mucida D., Kutchukhidze N., Erazo A., Russo M., Lafaille J.J., and Curotto de Lafaille M.A. Oral tolerance in the absence of naturally occurring Tregs. J. Clin. Invest. 115 (2005) 1923-1933
42. Mucida D., Park Y., Kim G., Turovskaya O., Scott I., Kronenberg M., and Cheroutre H. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317 (2007) 256-260
43. Nurieva R., Yang X.O., Martinez G., Zhang Y., Panopoulos A.D., Ma L., Schluns K., Tian Q., Watowich S.S., Jetten A.M., and Dong C. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448 (2007) 480-483
44. Ott S.J., Musfeldt M., Wenderoth D.F., Hampe J., Brant O., Folsch U.R., Timmis K.N., and Schreiber S. Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 53 (2004) 685-693
45. Pamer E.G. Immune responses to commensal and environmental microbes. Nat. Immunol. 8 (2007) 1173-1178
46. Pasare C., and Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 299 (2003) 1033-1036
47. Pasare C., and Medzhitov R. Toll-dependent control mechanisms of CD4 T cell activation. Immunity 21 (2004) 733-741
48. Paulos C.M., Wrzesinski C., Kaiser A., Hinrichs C.S., Chieppa M., Cassard L., Palmer D.C., Boni A., Muranski P., Yu Z., et al. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling. J. Clin. Invest. 117 (2007) 2197-2204
49. Peng G., Guo Z., Kiniwa Y., Voo K.S., Peng W., Fu T., Wang D.Y., Li Y., Wang H.Y., and Wang R.F. Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Science 309 (2005) 1380-1384
50. Plitas G., Burt B.M., Nguyen H.M., Bamboat Z.M., and DeMatteo R.P. Toll-like receptor 9 inhibition reduces mortality in polymicrobial sepsis. J. Exp. Med. 205 (2008) 1277-1283
51. Rachmilewitz D., Karmeli F., Takabayashi K., Hayashi T., Leider-Trejo L., Lee J., Leoni L.M., and Raz E. Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis. Gastroenterology 122 (2002) 1428-1441
52. Rachmilewitz D., Katakura K., Karmeli F., Hayashi T., Reinus C., Rudensky B., Akira S., Takeda K., Lee J., Takabayashi K., and Raz E. Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology 126 (2004) 520-528
53. Rakoff-Nahoum S., Paglino J., Eslami-Varzaneh F., Edberg S., and Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118 (2004) 229-241
54. Sansonetti P.J., and Di Santo J.P. Debugging how bacteria manipulate the immune response. Immunity 26 (2007) 149-161
55. Schalasta G., and Doppler C. Inhibition of c-fos transcription and phosphorylation of the serum response factor by an inhibitor of phospholipase C-type reactions. Mol. Cell. Biol. 10 (1990) 5558-5561
56. Seksik P., Rigottier-Gois L., Gramet G., Sutren M., Pochart P., Marteau P., Jian R., and Dore J. Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon. Gut 52 (2003) 237-242
57. Siewert C., Menning A., Dudda J., Siegmund K., Lauer U., Floess S., Campbell D.J., Hamann A., and Huehn J. Induction of organ-selective CD4(+) regulatory T cell homing. Eur. J. Immunol. 37 (2007) 978-989
58. Stumhofer J.S., Laurence A., Wilson E.H., Huang E., Tato C.M., Johnson L.M., Villarino A.V., Huang Q., Yoshimura A., Sehy D., et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat. Immunol. 7 (2006) 937-945
59. Sun C.M., Hall J.A., Blank R.B., Bouladoux N., Oukka M., Mora J.R., and Belkaid Y. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J. Exp. Med. 204 (2007) 1775-1785
60. Sutmuller R.P., den Brok M.H., Kramer M., Bennink E.J., Toonen L.W., Kullberg B.J., Joosten L.A., Akira S., Netea M.G., and Adema G.J. Toll-like receptor 2 controls expansion and function of regulatory T cells. J. Clin. Invest. 116 (2006) 485-494
61. Sutmuller R.P., Morgan M.E., Netea M.G., Grauer O., and Adema G.J. Toll-like receptors on regulatory T cells: Expanding immune regulation. Trends Immunol. 27 (2006) 387-393
62. Swidsinski A., Weber J., Loening-Baucke V., Hale L.P., and Lochs H. Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J. Clin. Microbiol. 43 (2005) 3380-3389
63. Takeda K., Kaisho T., and Akira S. Toll-like receptors. Annu. Rev. Immunol. 21 (2003) 335-376
64. Torok H.P., Glas J., Tonenchi L., Bruennler G., Folwaczny M., and Folwaczny C. Crohn's disease is associated with a toll-like receptor-9 polymorphism. Gastroenterology 127 (2004) 365-366
65. Uematsu S., Fujimoto K., Jang M.H., Yang B.G., Jung Y.J., Nishiyama M., Sato S., Tsujimura T., Yamamoto M., Yokota Y., et al. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat. Immunol. 9 (2008) 769-776
66. Veldhoen M., Hocking R.J., Atkins C.J., Locksley R.M., and Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24 (2006) 179-189
67. Vijay-Kumar M., Sanders C.J., Taylor R.T., Kumar A., Aitken J.D., Sitaraman S.V., Neish A.S., Uematsu S., Akira S., Williams I.R., and Gewirtz A.T. Deletion of TLR5 results in spontaneous colitis in mice. J. Clin. Invest. 117 (2007) 3909-3921
68. Wei J., Duramad O., Perng O.A., Reiner S.L., Liu Y.J., and Qin F.X. Antagonistic nature of T helper 1/2 developmental programs in opposing peripheral induction of Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. USA 104 (2007) 18169-18174
69. Weiss L.M., and Vossbrinck C.R. Microsporidiosis: Molecular and diagnostic aspects. Adv. Parasitol. 40 (1998) 351-395
70. Wu W., Weigand L., Belkaid Y., and Mendez S. Immunomodulatory effects associated with a live vaccine against Leishmania major containing CpG oligodeoxynucleotides. Eur. J. Immunol. 36 (2006) 3238-3247
71. Zhou L., Ivanov I.I., Spolski R., Min R., Shenderov K., Egawa T., Levy D.E., Leonard W.J., and Littman D.R. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat. Immunol. 8 (2007) 967-974