Activation of Typhi-Specific Regulatory T Cells in Typhoid Disease in a Wild-Type . Typhi Challenge Model

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In this manuscript, we describe, for the first time, a potential role for regulatory T cells (Treg) as an important factor in determining disease outcome in humans following exposure to wild-type S. Typhi. We studied in considerable depth the modulation of Treg activation characteristics and their homing potential in the development of typhoid disease following a wild-type S. Typhi challenge in a unique human infection model. We show that S. Typhi-specific up-regulation of the gut homing molecule integrin α4β7 pre-challenge is associated with subsequent development of typhoid disease. We further demonstrate that increased S. Typhi-specific expression of molecules associated with Treg activation as well as distinct kinetics of the expression of key activation molecules involved in Treg function are present in volunteers diagnosed with typhoid disease. We also provide the first evidence that Treg can functionally suppress S. Typhi-specific CD8+ T cells in vitro. These intriguing results suggest that Treg are likely to play a role in the development of typhoid fever and potentially other enteric infections.

Vyšlo v časopise: Activation of Typhi-Specific Regulatory T Cells in Typhoid Disease in a Wild-Type . Typhi Challenge Model. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004914
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004914

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Zdroje

1. Crump JA, Luby SP, Mintz ED (2004) The global burden of typhoid fever. Bull World Health Organ 82: 346–353. 15298225

2. Buckle GC, Walker CL, Black RE (2012) Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010. J Glob Health 2: 010401. doi: 10.7189/jogh.02.010401 23198130

3. Bhutta ZA (1996) Impact of age and drug resistance on mortality in typhoid fever. Arch Dis Child 75: 214–217. 8976660

4. Rowe B, Ward LR, Threlfall EJ (1997) Multidrug-resistant Salmonella typhi: a worldwide epidemic. Clin Infect Dis 24 Suppl 1: S106–109. 8994789

5. Levine MM, Ferreccio C, Abrego P, Martin OS, Ortiz E, et al. (1999) Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine 17 Suppl 2: S22–27. 10506405

6. Sur D, Ochiai RL, Bhattacharya SK, Ganguly NK, Ali M, et al. (2009) A cluster-randomized effectiveness trial of Vi typhoid vaccine in India. N Engl J Med 361: 335–344. doi: 10.1056/NEJMoa0807521 19625715

7. Waddington CS, Darton TC, Jones C, Haworth K, Peters A, et al. (2014) An outpatient, ambulant-design, controlled human infection model using escalating doses of salmonella typhi challenge delivered in sodium bicarbonate solution. Clin Infect Dis 58: 1230–1240. doi: 10.1093/cid/ciu078 24519873

8. McArthur MA, Sztein MB (2012) Heterogeneity of multifunctional IL-17A producing S. Typhi-specific CD8+ T cells in volunteers following Ty21a typhoid immunization. PLoS One 7: e38408. doi: 10.1371/journal.pone.0038408 22679502

9. Salerno-Goncalves R, Fernandez-Vina M, Lewinsohn DM, Sztein MB (2004) Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. J Immunol 173: 5852–5862. 15494539

10. Salerno-Goncalves R, Pasetti MF, Sztein MB (2002) Characterization of CD8(+) effector T cell responses in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. J Immunol 169: 2196–2203. 12165550

11. Salerno-Goncalves R, Wahid R, Sztein MB (2005) Immunization of volunteers with Salmonella enterica serovar Typhi strain Ty21a elicits the oligoclonal expansion of CD8+ T cells with predominant Vbeta repertoires. Infect Immun 73: 3521–3530. 15908381

12. Salerno-Goncalves R, Wahid R, Sztein MB (2010) Ex Vivo kinetics of early and long-term multifunctional human leukocyte antigen E-specific CD8+ cells in volunteers immunized with the Ty21a typhoid vaccine. Clin Vaccine Immunol 17: 1305–1314. doi: 10.1128/CVI.00234-10 20660136

13. Salerno-Goncalves R, Wyant TL, Pasetti MF, Fernandez-Vina M, Tacket CO, et al. (2003) Concomitant induction of CD4+ and CD8+ T cell responses in volunteers immunized with Salmonella enterica serovar typhi strain CVD 908-htrA. J Immunol 170: 2734–2741. 12594304

14. Sztein MB (2007) Cell-mediated immunity and antibody responses elicited by attenuated Salmonella enterica Serovar Typhi strains used as live oral vaccines in humans. Clin Infect Dis 45 Suppl 1: S15–19. 17582562

15. Sztein MB, Salerno-Goncalves R, McArthur MA (2014) Complex adaptive immunity to enteric fevers in humans: lessons learned and the path forward. Front Immunol 5: 516. doi: 10.3389/fimmu.2014.00516 25386175

16. Wing K, Sakaguchi S (2010) Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 11: 7–13. doi: 10.1038/ni.1818 20016504

17. Sakaguchi S, Wing K, Miyara M (2007) Regulatory T cells—a brief history and perspective. Eur J Immunol 37 Suppl 1: S116–123. 17972355

18. Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T (2009) Regulatory T cells: how do they suppress immune responses? Int Immunol 21: 1105–1111. doi: 10.1093/intimm/dxp095 19737784

19. Dhamne C, Chung Y, Alousi AM, Cooper LJ, Tran DQ (2013) Peripheral and thymic foxp3(+) regulatory T cells in search of origin, distinction, and function. Front Immunol 4: 253. doi: 10.3389/fimmu.2013.00253 23986762

20. Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, et al. (2007) Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med 204: 2803–2812. 18025126

21. Koch MA, Tucker-Heard G, Perdue NR, Killebrew JR, Urdahl KB, et al. (2009) The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat Immunol 10: 595–602. doi: 10.1038/ni.1731 19412181

22. Yamazaki T, Yang XO, Chung Y, Fukunaga A, Nurieva R, et al. (2008) CCR6 regulates the migration of inflammatory and regulatory T cells. J Immunol 181: 8391–8401. 19050256

23. Engelhardt BG, Sengsayadeth SM, Jagasia M, Savani BN, Kassim AA, et al. (2012) Tissue-specific regulatory T cells: biomarker for acute graft-vs-host disease and survival. Exp Hematol 40: 974–982 e971. doi: 10.1016/j.exphem.2012.08.002 22885125

24. Li L, Lao SH, Wu CY (2007) Increased frequency of CD4(+)CD25(high) Treg cells inhibit BCG-specific induction of IFN-gamma by CD4(+) T cells from TB patients. Tuberculosis (Edinb) 87: 526–534. 17851131

25. Lyke KE, Dabo A, Arama C, Daou M, Diarra I, et al. (2012) Reduced T regulatory cell response during acute Plasmodium falciparum infection in Malian children co-infected with Schistosoma haematobium. PLoS One 7: e31647. doi: 10.1371/journal.pone.0031647 22348117

26. Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA (2001) CD4+CD25high regulatory cells in human peripheral blood. J Immunol 167: 1245–1253. 11466340

27. Presicce P, Moreno-Fernandez ME, Lages CS, Orsborn KI, Chougnet CA (2010) Association of two clones allows for optimal detection of human FOXP3. Cytometry A 77: 571–579. doi: 10.1002/cyto.a.20875 20162533

28. Mora JR, Iwata M, Eksteen B, Song SY, Junt T, et al. (2006) Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314: 1157–1160. 17110582

29. Wahid R, Salerno-Goncalves R, Tacket CO, Levine MM, Sztein MB (2008) Generation of specific effector and memory T cells with gut- and secondary lymphoid tissue- homing potential by oral attenuated CVD 909 typhoid vaccine in humans. Mucosal Immunol 1: 389–398. doi: 10.1038/mi.2008.30 19079203

30. Stagg AJ, Kamm MA, Knight SC (2002) Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin. Eur J Immunol 32: 1445–1454. 11981833

31. Witowski J, Ksiazek K, Jorres A (2004) Interleukin-17: a mediator of inflammatory responses. Cell Mol Life Sci 61: 567–579. 15004696

32. Kleinschek MA, Boniface K, Sadekova S, Grein J, Murphy EE, et al. (2009) Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation. J Exp Med 206: 525–534. doi: 10.1084/jem.20081712 19273624

33. Raffatellu M, Santos RL, Verhoeven DE, George MD, Wilson RP, et al. (2008) Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med 14: 421–428. doi: 10.1038/nm1743 18376406

34. Baecher-Allan C, Wolf E, Hafler DA (2006) MHC class II expression identifies functionally distinct human regulatory T cells. J Immunol 176: 4622–4631. 16585553

35. Ashley CW, Baecher-Allan C (2009) Cutting Edge: Responder T cells regulate human DR+ effector regulatory T cell activity via granzyme B. J Immunol 183: 4843–4847. doi: 10.4049/jimmunol.0900845 19801510

36. Tang Q, Henriksen KJ, Bi M, Finger EB, Szot G, et al. (2004) In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med 199: 1455–1465. 15184499

37. Fletcher JM, Lonergan R, Costelloe L, Kinsella K, Moran B, et al. (2009) CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol 183: 7602–7610. doi: 10.4049/jimmunol.0901881 19917691

38. Gupta S, Thornley TB, Gao W, Larocca R, Turka LA, et al. (2012) Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs. J Clin Invest 122: 2395–2404. doi: 10.1172/JCI45138 22684103

39. Duggleby RC, Shaw TN, Jarvis LB, Kaur G, Gaston JS (2007) CD27 expression discriminates between regulatory and non-regulatory cells after expansion of human peripheral blood CD4+ CD25+ cells. Immunology 121: 129–139. 17425604

40. Ruprecht CR, Gattorno M, Ferlito F, Gregorio A, Martini A, et al. (2005) Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia. J Exp Med 201: 1793–1803. 15939793

41. Koenen HJ, Fasse E, Joosten I (2005) CD27/CFSE-based ex vivo selection of highly suppressive alloantigen-specific human regulatory T cells. J Immunol 174: 7573–7583. 15944257

42. Yadav M, Stephan S, Bluestone JA (2013) Peripherally induced tregs—role in immune homeostasis and autoimmunity. Front Immunol 4: 232. doi: 10.3389/fimmu.2013.00232 23966994

43. Chaudhary B, Khaled YS, Ammori BJ, Elkord E (2014) Neuropilin 1: function and therapeutic potential in cancer. Cancer Immunol Immunother 63: 81–99. doi: 10.1007/s00262-013-1500-0 24263240

44. Johanns TM, Ertelt JM, Rowe JH, Way SS (2010) Regulatory T cell suppressive potency dictates the balance between bacterial proliferation and clearance during persistent Salmonella infection. PLoS Pathog 6: e1001043. doi: 10.1371/journal.ppat.1001043 20714351

45. Sztein MB, Tanner MK, Polotsky Y, Orenstein JM, Levine MM (1995) Cytotoxic T lymphocytes after oral immunization with attenuated vaccine strains of Salmonella typhi in humans. J Immunol 155: 3987–3993. 7561107