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Regulatory T‐cells in helminth infection: induction, function and therapeutic potential

White, Madeleine P. J., McManus, Caitlin M., Maizels, Rick M.·2020·Immunology
DOI 10.1111/imm.13190PMC PMC7341546
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Abstract

Summary: Helminth parasites infect an alarmingly large proportion of the world's population, primarily within tropical regions, and their ability to down‐modulate host immunity is key to their persistence. Helminths have developed multiple mechanisms that induce a state of hyporesponsiveness or immune suppression within the host; of particular interest are mechanisms that drive the induction of regulatory T‐cells (Tregs). Helminths actively induce Tregs either directly by secreting factors, such as the TGF‐β mimic Hp‐ TGM, or indirectly by interacting with bystander cell types such as dendritic cells and macrophages that then induce Tregs. Expansion of Tregs not only enhances parasite survival but, in cases such as filarial infection, Tregs also play a role in preventing parasite‐associated pathologies. Furthermore, Tregs generated during helminth infection have been associated with suppression of bystander immunopathologies in a range of inflammatory conditions such as allergy and autoimmune disease. In this review, we discuss evidence from natural and experimental infections that point to the pathways and molecules involved in helminth Treg induction, and postulate how parasite‐derived molecules and/or Tregs might be applied as anti‐inflammatory therapies in the future.

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Figure 1 Overview of events in Treg expansion by helminths. (1) Early expansion of natural regulatory T‐cells (nTreg) by helminths within the first 3–7 days. (2) Helminth excretory−secretory (ES) products induce naïve CD4+ T‐cells to become Tregs. (3) ES products polarize dendritic cells (DCs) towards a tolerogenic phenotype capable of inducing Tregs. (4) M2 macrophage polarization following IL‐33 release by damaged epithelium, which then induce Tregs through an undefined mechanism. (5) Helminth proximity to Peyer's patch (PP) causes Treg expansion. It is as yet unclear whether Treg events (1)−(4) occur in either or both the lamina propria of the small intestine and the draining mesenteric lymph nodes, and hence no distinction is made in this figure.
Figure 1 Overview of events in Treg expansion by helminths. (1) Early expansion of natural regulatory T‐cells (nTreg) by helminths within the first 3–7 days. (2) Helminth excretory−secretory (ES) products induce naïve CD4+ T‐cells to become Tregs. (3) ES products polarize dendritic cells (DCs) towards a tolerogenic phenotype capable of inducing Tregs. (4) M2 macrophage polarization following IL‐33 release by damaged epithelium, which then induce Tregs through an undefined mechanism. (5) Helminth proximity to Peyer's patch (PP) causes Treg expansion. It is as yet unclear whether Treg events (1)−(4) occur in either or both the lamina propria of the small intestine and the draining mesenteric lymph nodes, and hence no distinction is made in this figure.CC BY · PubMed Central
Figure 2 Tregs in response to helminth infection in different tissues. Liver, upregulation of GITR, CD103 and CTLA‐4 on Tregs in response to Schistosoma mansoni infection and exposure to eggs trapped in the liver; peritoneal cavity, CD103 and CTLA‐4 on Tregs are upregulated when infected with the filarial nematode Brugia malayi; large intestine, increase in CD103 expression on Tregs in mice carrying duodenal infection with Heligmosomoides polygyrus, Treg expression of RORγt and ST2 are as yet unknown during helminth infection; pleural cavity, Litomosoides sigmodontis infection upregulates ICOS, GITR, PD‐1 and CTLA‐4 expression on Tregs; spleen, S. mansoni infection increases the expression of GITR and CTLA‐4 on Tregs; small intestine, Trichinella spiralis infection induces high levels of CTLA‐4 expression on Tregs and H. polygyrus infection upregulates CD103 and CTLA‐4 as measured on Tregs in the mesenteric lymph nodes, a surrogate of the populations in the small intestine lamina propria. CTLA‐4, cytotoxic T‐lymphocyte‐associated protein 4; GITR, glucocorticoid‐induced tumour necrosis factor receptor; ICOS, inducible T‐cell co‐stimulator; PD‐1, programmed cell death protein 1; RORγt RAR‐related orphan receptor gamma.
Figure 2 Tregs in response to helminth infection in different tissues. Liver, upregulation of GITR, CD103 and CTLA‐4 on Tregs in response to Schistosoma mansoni infection and exposure to eggs trapped in the liver; peritoneal cavity, CD103 and CTLA‐4 on Tregs are upregulated when infected with the filarial nematode Brugia malayi; large intestine, increase in CD103 expression on Tregs in mice carrying duodenal infection with Heligmosomoides polygyrus, Treg expression of RORγt and ST2 are as yet unknown during helminth infection; pleural cavity, Litomosoides sigmodontis infection upregulates ICOS, GITR, PD‐1 and CTLA‐4 expression on Tregs; spleen, S. mansoni infection increases the expression of GITR and CTLA‐4 on Tregs; small intestine, Trichinella spiralis infection induces high levels of CTLA‐4 expression on Tregs and H. polygyrus infection upregulates CD103 and CTLA‐4 as measured on Tregs in the mesenteric lymph nodes, a surrogate of the populations in the small intestine lamina propria. CTLA‐4, cytotoxic T‐lymphocyte‐associated protein 4; GITR, glucocorticoid‐induced tumour necrosis factor receptor; ICOS, inducible T‐cell co‐stimulator; PD‐1, programmed cell death protein 1; RORγt RAR‐related orphan receptor gamma.CC BY · PubMed Central

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Research works printed but not linked: 128

  1. 10.1016/S0140-6736(18)32279-7 · DOI · Paper page
  2. 10.1186/1756-3305-7-37 · DOI
  3. 10.1111/pim.12193 · DOI
  4. 10.1111/cei.12353 · DOI
  5. 10.1016/j.jaci.2006.03.003 · DOI
  6. 10.1177/1757913916650225 · DOI
  7. 10.1016/j.ijpara.2012.11.011 · DOI
  8. 10.1146/annurev-immunol-042718-041717 · DOI
  9. 10.1016/j.immuni.2013.03.002 · DOI
  10. 10.1111/j.1600-065X.2011.01017.x · DOI
  11. 10.4269/ajtmh.2007.77.676 · DOI
  12. 10.4049/jimmunol.0904067 · DOI
  13. 10.1371/journal.pntd.0001655 · DOI
  14. 10.1371/journal.pntd.0000420 · DOI
  15. 10.1371/journal.pntd.0003414 · DOI
  16. 10.1126/scitranslmed.aaw3703 · DOI
  17. 10.1002/eji.200838193 · DOI
  18. 10.1126/science.1144603 · DOI
  19. 10.1016/j.micinf.2005.03.036 · DOI
  20. 10.1093/infdis/173.5.1242 · DOI
  21. 10.1093/infdis/172.6.1567 · DOI
  22. 10.1016/j.vaccine.2008.04.083 · DOI
  23. 10.1002/eji.200939699 · DOI
  24. 10.1002/eji.201545843 · DOI
  25. 10.1002/eji.200636751 · DOI
  26. 10.4049/jimmunol.181.9.6456 · DOI
  27. 10.1128/IAI.01233-07 · DOI
  28. 10.1002/eji.200838727 · DOI
  29. 10.4049/jimmunol.1001920 · DOI
  30. 10.1038/mi.2015.73 · DOI
  31. 10.1128/IAI.73.7.4034-4042.2005 · DOI
  32. 10.4049/jimmunol.174.8.4924 · DOI · Paper page
  33. 10.1007/s00436-010-2089-2 · DOI
  34. 10.1002/eji.200737063 · DOI
  35. 10.4049/jimmunol.178.2.1039 · DOI
  36. 10.4049/jimmunol.0802767 · DOI
  37. 10.1016/j.exppara.2013.11.001 · DOI
  38. 10.4049/jimmunol.179.7.4626 · DOI
  39. 10.1002/eji.200939644 · DOI
  40. 10.1371/journal.ppat.1003913 · DOI
  41. 10.4049/jimmunol.1202502 · DOI · Paper page
  42. 10.1371/journal.pone.0125495 · DOI
  43. 10.1371/journal.pone.0125945 · DOI
  44. 10.1371/journal.ppat.1003675 · DOI
  45. 10.1002/eji.200939721 · DOI
  46. 10.1002/eji.201242794 · DOI
  47. 10.1128/IAI.00266-15 · DOI
  48. 10.1016/j.jprot.2011.06.002 · DOI
  49. 10.1038/s41467-017-01886-6 · DOI · Paper page
  50. 10.1002/eji.200838871 · DOI
  51. 10.1186/2045-3701-1-20 · DOI
  52. 10.1002/eji.201141429 · DOI
  53. 10.3389/fimmu.2018.00011 · DOI
  54. 10.1002/eji.200636553 · DOI
  55. 10.1016/j.coi.2014.09.004 · DOI
  56. 10.1038/ni.1852 · DOI
  57. 10.1038/ncomms14919 · DOI
  58. 10.1371/journal.ppat.1006649 · DOI
  59. 10.1111/j.1365-3024.2007.00947.x · DOI
  60. 10.4049/jimmunol.176.9.5374 · DOI
  61. 10.4049/jimmunol.172.5.3157 · DOI
  62. 10.3347/kjp.2016.54.2.163 · DOI
  63. 10.4049/jimmunol.1100834 · DOI
  64. 10.1038/ni.2683 · DOI
  65. 10.1038/s41590-019-0351-z · DOI
  66. 10.1038/nature13577 · DOI
  67. 10.1111/j.1365-2249.2010.04139.x · DOI
  68. 10.1016/j.coi.2005.09.001 · DOI
  69. 10.1159/000332949 · DOI · Paper page
  70. 10.1016/S0140-6736(00)03206-2 · DOI
  71. 10.1159/000024433 · DOI
  72. 10.1159/000088879 · DOI
  73. 10.1086/381767 · DOI · Paper page
  74. 10.1111/j.1365-2222.2009.03346.x · DOI · Paper page
  75. 10.1017/S0031182011001053 · DOI
  76. 10.1111/j.1399-3038.2010.01122.x · DOI
  77. 10.1111/j.1398-9995.2010.02512.x · DOI · Paper page
  78. 10.4269/ajtmh.16-0348 · DOI
  79. 10.1016/j.jaci.2007.06.009 · DOI
  80. 10.1371/journal.pone.0019149 · DOI
  81. 10.1002/ana.21067 · DOI
  82. 10.1016/j.jneuroim.2011.01.002 · DOI · Paper page
  83. 10.1128/IAI.73.9.5468-5481.2005 · DOI
  84. 10.1164/ajrccm.156.1.9606081 · DOI
  85. 10.3389/fimmu.2017.00453 · DOI
  86. 10.1016/j.coi.2018.05.007 · DOI
  87. 10.1016/j.jaci.2016.07.007 · DOI · Paper page
  88. 10.1084/jem.20042572 · DOI
  89. 10.1111/j.1365-2222.2009.03290.x · DOI
  90. 10.4049/jimmunol.177.3.1628 · DOI
  91. 10.4049/jimmunol.176.1.138 · DOI
  92. 10.1371/journal.pntd.0002379 · DOI · Paper page
  93. 10.1016/S0140-6736(76)92492-2 · DOI
  94. 10.1126/scitranslmed.3001500 · DOI
  95. 10.1371/journal.ppat.1003000 · DOI
  96. 10.1136/gut.2004.041749 · DOI · Paper page
  97. 10.1053/j.gastro.2005.01.005 · DOI · Paper page
  98. 10.1016/j.jaci.2014.07.007 · DOI
  99. 10.1007/7854_2014_361 · DOI
  100. 10.1016/S1473-3099(14)70771-6 · DOI
  101. 10.1111/pim.12175 · DOI
  102. 10.1186/s12865-015-0074-3 · DOI · Paper page
  103. 10.1016/j.trsl.2015.06.016 · DOI
  104. 10.1017/S0022149X16000316 · DOI
  105. Garg SK, 2014, Helminth therapy (worms) for induction of remission in inflammatory bowel disease, Cochrane Database Syst Rev, 1, CD009400
  106. Scholmerich J, 2017, A randomised, double‐blind, placebo‐controlled trial of Trichuris suis ova in active Crohn's disease, J Crohns Colitis, 11, 390
  107. Fleming J, 2014, Clinical trial of helminth‐induced immunomodulatory therapy (HINT 2) in relapsing‐remitting multiple sclerosis, Neurology, 82, 149
  108. 10.1016/j.jaci.2014.07.022 · DOI
  109. 10.1371/journal.pone.0024092 · DOI
  110. 10.1128/CMR.05040-11 · DOI · Paper page
  111. 10.1038/cti.2017.42 · DOI
  112. 10.1016/S0020-7519(03)00163-2 · DOI
  113. 10.3389/fimmu.2019.02280 · DOI · Paper page
  114. 10.1038/s41577-019-0232-6 · DOI
  115. 10.3324/haematol.2012.074088 · DOI
  116. 10.1016/j.coi.2013.12.005 · DOI
  117. 10.1002/eji.201040391 · DOI
  118. 10.4049/jimmunol.180.11.7112 · DOI
  119. 10.1073/pnas.1408780111 · DOI
  120. 10.3389/fimmu.2019.00043 · DOI · Paper page
  121. 10.1016/j.diagmicrobio.2008.06.015 · DOI
  122. 10.1371/journal.pntd.0001383 · DOI
  123. 10.1371/journal.pntd.0003995 · DOI
  124. 10.1371/journal.pntd.0000456 · DOI
  125. 10.1371/journal.pntd.0007415 · DOI
  126. 10.1645/GE-2839.1 · DOI
  127. 10.4049/jimmunol.179.7.4626 · DOI
  128. 10.1371/journal.pntd.0001269 · DOI

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Metadata

Authors
White, M. P. J., McManus, C. M., & Maizels, R. M.
Venue
Immunology
Publisher
Wiley
Published
2020-04-19
Volume
160
Issue
3
Pages
248-260
ISSN
  • 0019-2805
  • 1365-2567
DOI
10.1111/imm.13190
PMC
PMC7341546
Cited by
114
References
8
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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CoChat. (2026). Citation check: Regulatory T‐cells in helminth infection: induction, function and therapeutic potential. https://app.cochat.ai/papers/10.1111/imm.13190
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White, M. P. J., McManus, C. M., & Maizels, R. M. (2020). Regulatory T‐cells in helminth infection: induction, function and therapeutic potential. Immunology. https://doi.org/10.1111/imm.13190