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Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4(+)CD25(+) T Regulatory Cells
OBJECTIVE: To examine if the protective effect of parasite infection on experimental autoimmune encephalomyelitis (EAE) was due to interleukin (IL)-5, a cytokine produced by a type-2 response that induces eosinophilia. We hypothesize that, in parasite infections, IL-5 also promotes expansion of anti...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671975/ https://www.ncbi.nlm.nih.gov/pubmed/29163523 http://dx.doi.org/10.3389/fimmu.2017.01453 |
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author | Tran, Giang T. Wilcox, Paul L. Dent, Lindsay A. Robinson, Catherine M. Carter, Nicole Verma, Nirupama D. Hall, Bruce M. Hodgkinson, Suzanne J. |
author_facet | Tran, Giang T. Wilcox, Paul L. Dent, Lindsay A. Robinson, Catherine M. Carter, Nicole Verma, Nirupama D. Hall, Bruce M. Hodgkinson, Suzanne J. |
author_sort | Tran, Giang T. |
collection | PubMed |
description | OBJECTIVE: To examine if the protective effect of parasite infection on experimental autoimmune encephalomyelitis (EAE) was due to interleukin (IL)-5, a cytokine produced by a type-2 response that induces eosinophilia. We hypothesize that, in parasite infections, IL-5 also promotes expansion of antigen-specific T regulatory cells that control autoimmunity. METHODS: Nippostrongylus brasiliensis larvae were used to infect Lewis rats prior to induction of EAE by myelin basic protein. Animals were sham treated, or given blocking monoclonal antibodies to interleukin 4 or 5 or to deplete CD25(+) T cells. Reactivity of CD4(+)CD25(+) T regulatory cells from these animals was examined. RESULTS: Parasite-infected hosts had reduced severity and length of EAE. The beneficial effect of parasitic infection was abolished with an anti-IL-5 or an anti-CD25 monoclonal antibody (mAb), but not anti-IL-4 mAb. Parasite-infected animals with EAE developed antigen-specific CD4(+)CD25(+) T regulatory cells earlier than EAE controls and these expressed more Il5ra than controls. Treatment with IL-5 also reduced the severity of EAE and induced Il5ra expressing CD4(+)CD25(+) T regulatory cells. INTERPRETATION: The results of this study suggested that IL-5 produced by the type-2 inflammatory response to parasite infection promoted induction of autoantigen-specific CD25(+)Il5ra(+) T regulatory cells that reduced the severity of autoimmunity. Such a mechanism may explain the protective effect of parasite infection in patients with multiple sclerosis where eosinophilia is induced by IL-5, produced by the immune response to parasites. |
format | Online Article Text |
id | pubmed-5671975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56719752017-11-21 Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4(+)CD25(+) T Regulatory Cells Tran, Giang T. Wilcox, Paul L. Dent, Lindsay A. Robinson, Catherine M. Carter, Nicole Verma, Nirupama D. Hall, Bruce M. Hodgkinson, Suzanne J. Front Immunol Immunology OBJECTIVE: To examine if the protective effect of parasite infection on experimental autoimmune encephalomyelitis (EAE) was due to interleukin (IL)-5, a cytokine produced by a type-2 response that induces eosinophilia. We hypothesize that, in parasite infections, IL-5 also promotes expansion of antigen-specific T regulatory cells that control autoimmunity. METHODS: Nippostrongylus brasiliensis larvae were used to infect Lewis rats prior to induction of EAE by myelin basic protein. Animals were sham treated, or given blocking monoclonal antibodies to interleukin 4 or 5 or to deplete CD25(+) T cells. Reactivity of CD4(+)CD25(+) T regulatory cells from these animals was examined. RESULTS: Parasite-infected hosts had reduced severity and length of EAE. The beneficial effect of parasitic infection was abolished with an anti-IL-5 or an anti-CD25 monoclonal antibody (mAb), but not anti-IL-4 mAb. Parasite-infected animals with EAE developed antigen-specific CD4(+)CD25(+) T regulatory cells earlier than EAE controls and these expressed more Il5ra than controls. Treatment with IL-5 also reduced the severity of EAE and induced Il5ra expressing CD4(+)CD25(+) T regulatory cells. INTERPRETATION: The results of this study suggested that IL-5 produced by the type-2 inflammatory response to parasite infection promoted induction of autoantigen-specific CD25(+)Il5ra(+) T regulatory cells that reduced the severity of autoimmunity. Such a mechanism may explain the protective effect of parasite infection in patients with multiple sclerosis where eosinophilia is induced by IL-5, produced by the immune response to parasites. Frontiers Media S.A. 2017-11-01 /pmc/articles/PMC5671975/ /pubmed/29163523 http://dx.doi.org/10.3389/fimmu.2017.01453 Text en Copyright © 2017 Tran, Wilcox, Dent, Robinson, Carter, Verma, Hall and Hodgkinson. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Tran, Giang T. Wilcox, Paul L. Dent, Lindsay A. Robinson, Catherine M. Carter, Nicole Verma, Nirupama D. Hall, Bruce M. Hodgkinson, Suzanne J. Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4(+)CD25(+) T Regulatory Cells |
title | Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4(+)CD25(+) T Regulatory Cells |
title_full | Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4(+)CD25(+) T Regulatory Cells |
title_fullStr | Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4(+)CD25(+) T Regulatory Cells |
title_full_unstemmed | Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4(+)CD25(+) T Regulatory Cells |
title_short | Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4(+)CD25(+) T Regulatory Cells |
title_sort | interleukin-5 mediates parasite-induced protection against experimental autoimmune encephalomyelitis: association with induction of antigen-specific cd4(+)cd25(+) t regulatory cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671975/ https://www.ncbi.nlm.nih.gov/pubmed/29163523 http://dx.doi.org/10.3389/fimmu.2017.01453 |
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