Foxp3+ Regulatory T Cells Delay Expulsion of Intestinal Nematodes by Suppression of IL-9-Driven Mast Cell Activation in BALB/c but Not in C57BL/6 Mice

PLoS Pathogens

Volumn 10, Issue 2, 2014, Pages

  Blankenhaus, Birte ^a   Reitz, Martina ^a   Brenz, Yannick ^a   Eschbach, Marie Luise ^a   Hartmann, Wiebke ^a   Haben, Irma ^a   Sparwasser, Tim ^b   Huehn, Jochen ^c   Kühl, Anja ^d   Feyerabend, Thorsten B ^e   Rodewald, Hans Reimer ^e   Breloer, Minka ^a  

^a BERNHARD NOCHT INSTITUTE FOR TROPICAL MEDICINE   (Germany)

^b HANNOVER MEDICAL SCHOOL   (Germany)

^c HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^d CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^e GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD103 ANTIGEN; CHYMASE; HELIOS PROTEIN; IMMUNOGLOBULIN E; IMMUNOGLOBULIN M; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 2; INTERLEUKIN 3; INTERLEUKIN 4; INTERLEUKIN 9; NEUROPILIN; PEPTIDES AND PROTEINS; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CD4+ T LYMPHOCYTE; CELL ACTIVATION; CELLULAR IMMUNITY; CONTROLLED STUDY; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; IMMUNOLOGICAL PROCEDURES; LARVA; LYMPHOCYTE DEPLETION; MAST CELL; MAST CELL DEGRANULATION; MOUSE; NEMATODIASIS; NEUTROPHILIA; NONHUMAN; PARASITE LOAD; REGULATORY T LYMPHOCYTE; STRONGYLOIDIASIS; TREG DEPLETION;

ANIMALS; CELL DEGRANULATION; ENZYME-LINKED IMMUNOSORBENT ASSAY; FORKHEAD TRANSCRIPTION FACTORS; INTERLEUKIN-9; MAST CELLS; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; STRONGYLOIDES RATTI; STRONGYLOIDIASIS; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY;

EID: 84895738894     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003913     Document Type: Article

References (77)

1. McSorley HJ, Maizels RM, (2012) Helminth infections and host immune regulation. Clin Microbiol Rev 25: 585-608.
2. Maizels RM, Balic A, Gomez-Escobar N, Nair M, Taylor MD, et al. (2004) Helminth parasites-masters of regulation. Immunol Rev 201: 89-116.
3. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M, (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. Journal of Immunology 155: 1151-1164.
4. Wing K, Sakaguchi S, (2010) Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 11: 7-13.
5. Wammes LJ, Hamid F, Wiria AE, Wibowo H, Sartono E, et al. (2012) Regulatory T cells in human lymphatic filariasis: stronger functional activity in microfilaremics. PLoS Negl Trop Dis 6: e1655.
6. Wammes LJ, Hamid F, Wiria AE, de Gier B, Sartono E, et al. (2010) Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparum. Eur J Immunol 40: 437-442.
7. Metenou S, Dembele B, Konate S, Dolo H, Coulibaly SY, et al. (2010) At homeostasis filarial infections have expanded adaptive T regulatory but not classical Th2 cells. J Immunol 184: 5375-5382.
8. Nausch N, Midzi N, Mduluza T, Maizels RM, Mutapi F, (2011) Regulatory and activated T cells in human Schistosoma haematobium infections. PLoS ONE 6: e16860.
9. Montes M, Sanchez C, Verdonck K, Lake JE, Gonzalez E, et al. (2009) Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen. PLoS Negl Trop Dis 3: e456.
10. Finney CA, Taylor MD, Wilson MS, Maizels RM, (2007) Expansion and activation of CD4(+)CD25(+) regulatory T cells in Heligmosomoides polygyrus infection. Eur J Immunol 37: 1874-1886.
11. McSorley HJ, Harcus YM, Murray J, Taylor MD, Maizels RM, (2008) Expansion of Foxp3+ regulatory T cells in mice infected with the filarial parasite Brugia malayi. J Immunol 181: 6456-6466.
12. Rausch S, Huehn J, Kirchhoff D, Rzepecka J, Schnoeller C, et al. (2008) Functional analysis of effector and regulatory T cells in a parasitic nematode infection. Infect Immun 76: 1908-1919.
13. Taylor MD, van der Werf N, Harris A, Graham AL, Bain O, et al. (2009) Early recruitment of natural CD4+ Foxp3+ Treg cells by infective larvae determines the outcome of filarial infection. Eur J Immunol 39: 192-206.
14. Blankenhaus B, Klemm U, Eschbach ML, Sparwasser T, Huehn J, et al. (2011) Strongyloides ratti infection induces expansion of Foxp3+ regulatory T cells that interfere with immune response and parasite clearance in BALB/c mice. Journal of Immunology 186: 4295-4305.
15. Grainger JR, Smith KA, Hewitson JP, McSorley HJ, Harcus Y, et al. (2010) Helminth secretions induce de novo T cell Foxp3 expression and regulatory function through the TGF-beta pathway. J Exp Med 207: 2331-2341.
16. Taylor JJ, Mohrs M, Pearce EJ, (2006) Regulatory T cell responses develop in parallel to Th responses and control the magnitude and phenotype of the Th effector population. J Immunol 176: 5839-5847.
17. Layland LE, Rad R, Wagner H, da Costa CU, (2007) Immunopathology in schistosomiasis is controlled by antigen-specific regulatory T cells primed in the presence of TLR2. Eur J Immunol 37: 2174-2184.
18. Rausch S, Huehn J, Loddenkemper C, Hepworth MR, Klotz C, et al. (2009) Establishment of nematode infection despite increased Th2 responses and immunopathology after selective depletion of Foxp3+ cells. Eur J Immunol 39: 3066-3077.
19. D'Elia R, Behnke JM, Bradley JE, Else KJ, (2009) Regulatory T cells: a role in the control of helminth-driven intestinal pathology and worm survival. J Immunol 182: 2340-2348.
20. Wilson MS, Taylor MD, Balic A, Finney CA, Lamb JR, et al. (2005) Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med 202: 1199-1212.
21. Dittrich AM, Erbacher A, Specht S, Diesner F, Krokowski M, et al. (2008) Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model. J Immunol 180: 1792-1799.
22. Tetsutani K, Ishiwata K, Ishida H, Tu L, Torii M, et al. (2009) Concurrent infection with Heligmosomoides polygyrus suppresses anti-Plasmodium yoelii protection partially by induction of CD4(+)CD25(+)Foxp3(+) Treg in mice. Eur J Immunol 39: 2822-2830.
23. Pacifico LG, Marinho FA, Fonseca CT, Barsante MM, Pinho V, et al. (2009) Schistosoma mansoni antigens modulate experimental allergic asthma in a murine model: a major role for CD4+ CD25+ Foxp3+ T cells independent of interleukin-10. Infect Immun 77: 98-107.
24. Taylor MD, van der Werf N, Maizels RM, (2012) T cells in helminth infection: the regulators and the regulated. Trends Immunol 33: 181-189.
25. Fontenot JD, Gavin MA, Rudensky AY, (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4: 330-336.
26. Lahl K, Loddenkemper C, Drouin C, Freyer J, Arnason J, et al. (2007) Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med 204: 57-63.
27. Kim JM, Rasmussen JP, Rudensky AY, (2007) Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol 8: 191-197.
28. Lahl K, Sparwasser T, (2011) In vivo depletion of FoxP3+ Tregs using the DEREG mouse model. Methods in molecular biology 707: 157-172.
29. Viney ME, Lok JB (2007) Strongyloides spp. WormBook doi/10.1895/wormbook.1.141.1.available at http://www.wormbook.org.: 1-15.
30. Uchikawa R, Nojima H, Sato A, (1989) The effects of single and repeated inoculations of various larval doses on Strongyloides ratti burden and distribution in rats. J Parasitol 75: 577-584.
31. Dawkins HJ, Grove DI, (1981) Kinetics of primary and secondary infections with Strongyloides ratti in mice. Int J Parasitol 11: 89-96.
32. Wilkes CP, Bleay C, Paterson S, Viney ME, (2007) The immune response during a Strongyloides ratti infection of rats. Parasite Immunol 29: 339-346.
33. Eschbach ML, Klemm U, Kolbaum J, Blankenhaus B, Brattig N, et al. (2010) Strongyloides ratti infection induces transient nematode-specific Th2 response and reciprocal suppression of IFN-gamma production in mice. Parasite immunology 32: 370-383.
34. Watanabe K, Noda K, Hamano S, Koga M, Kishihara K, et al. (2000) The crucial role of granulocytes in the early host defense against Strongyloides ratti infection in mice. Parasitol Res 86: 188-193.
35. Galioto AM, Hess JA, Nolan TJ, Schad GA, Lee JJ, et al. (2006) Role of eosinophils and neutrophils in innate and adaptive protective immunity to larval strongyloides stercoralis in mice. Infect Immun 74: 5730-5738.
36. Kerepesi LA, Hess JA, Nolan TJ, Schad GA, Abraham D, (2006) Complement component C3 is required for protective innate and adaptive immunity to larval strongyloides stercoralis in mice. J Immunol 176: 4315-4322.
37. Brigandi RA, Rotman HL, Yutanawiboonchai W, Leon O, Nolan TJ, et al. (1996) Strongyloides stercoralis: role of antibody and complement in immunity to the third stage of larvae in BALB/cByJ mice. Exp Parasitol 82: 279-289.
38. Nawa Y, Kiyota M, Korenaga M, Kotani M, (1985) Defective protective capacity of W/Wv mice against Strongyloides ratti infection and its reconstitution with bone marrow cells. Parasite Immunol 7: 429-438.
39. Fukao T, Yamada T, Tanabe M, Terauchi Y, Ota T, et al. (2002) Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice. Nat Immunol 3: 295-304.
40. Sasaki Y, Yoshimoto T, Maruyama H, Tegoshi T, Ohta N, et al. (2005) IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity. J Exp Med 202: 607-616.
41. Rodewald HR, Feyerabend TB, (2012) Widespread immunological functions of mast cells: fact or fiction? Immunity 37: 13-24.
42. Licona-Limon P, Henao-Mejia J, Temann AU, Gagliani N, Licona-Limon I, et al. (2013) Th9 Cells Drive Host Immunity against Gastrointestinal Worm Infection. Immunity 39: 744-757.
43. Turner JE, Morrison PJ, Wilhelm C, Wilson M, Ahlfors H, et al. (2013) IL-9-mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation. J Exp Med.
44. Huehn J, Siegmund K, Lehmann JC, Siewert C, Haubold U, et al. (2004) Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells. J Exp Med 199: 303-313.
45. Sugimoto N, Oida T, Hirota K, Nakamura K, Nomura T, et al. (2006) Foxp3-dependent and-independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. International immunology 18: 1197-1209.
46. Weiss JM, Bilate AM, Gobert M, Ding Y, Curotto de Lafaille MA, et al. (2012) Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells. J Exp Med 209: 1723-1742, S1721.
47. Yadav M, Louvet C, Davini D, Gardner JM, Martinez-Llordella M, et al. (2012) Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J Exp Med 209: 1713-1719, 1713-1722, S1711-1719.
48. Khan AI, Horii Y, Tiuria R, Sato Y, Nawa Y, (1993) Mucosal mast cells and the expulsive mechanisms of mice against Strongyloides venezuelensis. Int J Parasitol 23: 551-555.
49. Reynolds DS, Stevens RL, Lane WS, Carr MH, Austen KF, et al. (1990) Different mouse mast cell populations express various combinations of at least six distinct mast cell serine proteases. Proc Natl Acad Sci U S A 87: 3230-3234.
50. Tittel AP, Heuser C, Ohliger C, Llanto C, Yona S, et al. (2012) Functionally relevant neutrophilia in CD11c diphtheria toxin receptor transgenic mice. Nature methods 9: 385-390.
51. Machado ER, Carlos D, Lourenco EV, Sorgi CA, Silva EV, et al. (2009) Counterregulation of Th2 immunity by interleukin 12 reduces host defenses against Strongyloides venezuelensis infection. Microbes Infect 11: 571-578.
52. Bonne-Annee S, Hess JA, Abraham D, (2011) Innate and adaptive immunity to the nematode Strongyloides stercoralis in a mouse model. Immunologic research 51: 205-214.
53. Lantz CS, Boesiger J, Song CH, Mach N, Kobayashi T, et al. (1998) Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392: 90-93.
54. Abe T, Sugaya H, Ishida K, Khan WI, Tasdemir I, et al. (1993) Intestinal protection against Strongyloides ratti and mastocytosis induced by administration of interleukin-3 in mice. Immunology 80: 116-121.
55. Noelle RJ, Nowak EC, (2010) Cellular sources and immune functions of interleukin-9. Nature reviews Immunology 10: 683-687.
56. Townsend JM, Fallon GP, Matthews JD, Smith P, Jolin EH, et al. (2000) IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity 13: 573-583.
57. Faulkner H, Renauld JC, Van Snick J, Grencis RK, (1998) Interleukin-9 enhances resistance to the intestinal nematode Trichuris muris. Infection and immunity 66: 3832-3840.
58. Faulkner H, Humphreys N, Renauld JC, Van Snick J, Grencis R, (1997) Interleukin-9 is involved in host protective immunity to intestinal nematode infection. European Journal of Immunology 27: 2536-2540.
59. Richard M, Grencis RK, Humphreys NE, Renauld JC, Van Snick J, (2000) Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice. Proc Natl Acad Sci U S A 97: 767-772.
60. Khan WI, Richard M, Akiho H, Blennerhasset PA, Humphreys NE, et al. (2003) Modulation of intestinal muscle contraction by interleukin-9 (IL-9) or IL-9 neutralization: correlation with worm expulsion in murine nematode infections. Infection and immunity 71: 2430-2438.
61. Feyerabend TB, Weiser A, Tietz A, Stassen M, Harris N, et al. (2011) Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity. Immunity 35: 832-844.
62. Katz HR, Austen KF, (2011) Mast cell deficiency, a game of kit and mouse. Immunity 35: 668-670.
63. Michel A, Schuler A, Friedrich P, Doner F, Bopp T, et al. (2013) Mast cell-deficient Kit(W-sh) "Sash" mutant mice display aberrant myelopoiesis leading to the accumulation of splenocytes that act as myeloid-derived suppressor cells. Journal of Immunology 190: 5534-5544.
64. Antsiferova M, Martin C, Huber M, Feyerabend TB, Forster A, et al. (2013) Mast Cells Are Dispensable for Normal and Activin-Promoted Wound Healing and Skin Carcinogenesis. Journal of Immunology 191: 6147-55.
65. Gomez-Pinilla PJFG, Giovangiulio MD, Stakenborg N, Nemethova A, de Vries A, et al. (2014) Mast cells play no role in the pathogenesis of postoperative ileus induced by intestinal manipulation. PLOS One in press.
66. Gri G, Piconese S, Frossi B, Manfroi V, Merluzzi S, et al. (2008) CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity 29: 771-781.
67. Eller K, Wolf D, Huber JM, Metz M, Mayer G, et al. (2011) IL-9 production by regulatory T cells recruits mast cells that are essential for regulatory T cell-induced immune suppression. Journal of Immunology 186: 83-91.
68. Lu LF, Lind EF, Gondek DC, Bennett KA, Gleeson MW, et al. (2006) Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature 442: 997-1002.
69. Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, et al. (2008) Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 9: 1341-1346.
70. Wilhelm C, Hirota K, Stieglitz B, Van Snick J, Tolaini M, et al. (2011) An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation. Nat Immunol 12: 1071-1077.
71. Godfraind C, Louahed J, Faulkner H, Vink A, Warnier G, et al. (1998) Intraepithelial infiltration by mast cells with both connective tissue-type and mucosal-type characteristics in gut, trachea, and kidneys of IL-9 transgenic mice. Journal of Immunology 160: 3989-3996.
72. Chen X, Oppenheim JJ, Howard OM, (2005) BALB/c mice have more CD4+CD25+ T regulatory cells and show greater susceptibility to suppression of their CD4+CD25- responder T cells than C57BL/6 mice. J Leukoc Biol 78: 114-121.
73. Morampudi V, De Craeye S, Le Moine A, Detienne S, Braun MY, et al. (2011) Partial depletion of CD4(+)CD25(+)Foxp3(+) T regulatory cells significantly increases morbidity during acute phase Toxoplasma gondii infection in resistant BALB/c mice. Microbes and infection/Institut Pasteur 13: 394-404.
74. Paula MO, Fonseca DM, Wowk PF, Gembre AF, Fedatto PF, et al. (2011) Host genetic background affects regulatory T-cell activity that influences the magnitude of cellular immune response against Mycobacterium tuberculosis. Immunol Cell Biol 89: 526-534.
75. Forbes EE, Groschwitz K, Abonia JP, Brandt EB, Cohen E, et al. (2008) IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. J Exp Med 205: 897-913.
76. Brandt EB, Strait RT, Hershko D, Wang Q, Muntel EE, et al. (2003) Mast cells are required for experimental oral allergen-induced diarrhea. The Journal of clinical investigation 112: 1666-1677.
77. Nouir NB, Eschbach ML, Piedavent M, Osterloh A, Kingsley MT, et al. (2012) Vaccination with Strongyloides ratti heat shock protein 60 increases susceptibility to challenge infection by induction of Th1 response. Vaccine 30: 862-871.