CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel.
BACKGROUND:Chronic schistosomiasis is associated with T cell hypo-responsiveness and immunoregulatory mechanisms, including induction of regulatory T cells (Tregs). However, little is known about Treg functional capacity during human Schistosoma haematobium infection. METHODOLOGY:CD4+CD25hiFOXP3+ ce...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-08-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC4546370?pdf=render |
| _version_ | 1818334286791573504 |
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| author | Yvonne Schmiedel Ghyslain Mombo-Ngoma Lucja A Labuda Jacqueline J Janse Brechje de Gier Ayôla A Adegnika Saadou Issifou Peter G Kremsner Hermelijn H Smits Maria Yazdanbakhsh |
| author_facet | Yvonne Schmiedel Ghyslain Mombo-Ngoma Lucja A Labuda Jacqueline J Janse Brechje de Gier Ayôla A Adegnika Saadou Issifou Peter G Kremsner Hermelijn H Smits Maria Yazdanbakhsh |
| author_sort | Yvonne Schmiedel |
| collection | DOAJ |
| description | BACKGROUND:Chronic schistosomiasis is associated with T cell hypo-responsiveness and immunoregulatory mechanisms, including induction of regulatory T cells (Tregs). However, little is known about Treg functional capacity during human Schistosoma haematobium infection. METHODOLOGY:CD4+CD25hiFOXP3+ cells were characterized by flow cytometry and their function assessed by analysing total and Treg-depleted PBMC responses to schistosomal adult worm antigen (AWA), soluable egg antigen (SEA) and Bacillus Calmette-Guérin (BCG) in S. haematobium-infected Gabonese children before and 6 weeks after anthelmintic treatment. Cytokines responses (IFN-γ, IL-5, IL-10, IL-13, IL-17 and TNF) were integrated using Principal Component Analysis (PCA). Proliferation was measured by CFSE. PRINCIPAL FINDINGS:S. haematobium infection was associated with increased Treg frequencies, which decreased post-treatment. Cytokine responses clustered into two principal components reflecting regulatory and Th2-polarized (PC1) and pro-inflammatory and Th1-polarized (PC2) cytokine responses; both components increased post-treatment. Treg depletion resulted in increased PC1 and PC2 at both time-points. Proliferation on the other hand, showed no significant difference from pre- to post-treatment. Treg depletion resulted mostly in increased proliferative responses at the pre-treatment time-point only. CONCLUSIONS:Schistosoma-associated CD4+CD25hiFOXP3+Tregs exert a suppressive effect on both proliferation and cytokine production. Although Treg frequency decreases after praziquantel treatment, their suppressive capacity remains unaltered when considering cytokine production whereas their influence on proliferation weakens with treatment. |
| first_indexed | 2024-12-13T14:05:07Z |
| format | Article |
| id | doaj.art-afc75643e3364643b29240dfa1944765 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-13T14:05:07Z |
| publishDate | 2015-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-afc75643e3364643b29240dfa19447652022-12-21T23:42:38ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352015-08-0198e000399510.1371/journal.pntd.0003995CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel.Yvonne SchmiedelGhyslain Mombo-NgomaLucja A LabudaJacqueline J JanseBrechje de GierAyôla A AdegnikaSaadou IssifouPeter G KremsnerHermelijn H SmitsMaria YazdanbakhshBACKGROUND:Chronic schistosomiasis is associated with T cell hypo-responsiveness and immunoregulatory mechanisms, including induction of regulatory T cells (Tregs). However, little is known about Treg functional capacity during human Schistosoma haematobium infection. METHODOLOGY:CD4+CD25hiFOXP3+ cells were characterized by flow cytometry and their function assessed by analysing total and Treg-depleted PBMC responses to schistosomal adult worm antigen (AWA), soluable egg antigen (SEA) and Bacillus Calmette-Guérin (BCG) in S. haematobium-infected Gabonese children before and 6 weeks after anthelmintic treatment. Cytokines responses (IFN-γ, IL-5, IL-10, IL-13, IL-17 and TNF) were integrated using Principal Component Analysis (PCA). Proliferation was measured by CFSE. PRINCIPAL FINDINGS:S. haematobium infection was associated with increased Treg frequencies, which decreased post-treatment. Cytokine responses clustered into two principal components reflecting regulatory and Th2-polarized (PC1) and pro-inflammatory and Th1-polarized (PC2) cytokine responses; both components increased post-treatment. Treg depletion resulted in increased PC1 and PC2 at both time-points. Proliferation on the other hand, showed no significant difference from pre- to post-treatment. Treg depletion resulted mostly in increased proliferative responses at the pre-treatment time-point only. CONCLUSIONS:Schistosoma-associated CD4+CD25hiFOXP3+Tregs exert a suppressive effect on both proliferation and cytokine production. Although Treg frequency decreases after praziquantel treatment, their suppressive capacity remains unaltered when considering cytokine production whereas their influence on proliferation weakens with treatment.http://europepmc.org/articles/PMC4546370?pdf=render |
| spellingShingle | Yvonne Schmiedel Ghyslain Mombo-Ngoma Lucja A Labuda Jacqueline J Janse Brechje de Gier Ayôla A Adegnika Saadou Issifou Peter G Kremsner Hermelijn H Smits Maria Yazdanbakhsh CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel. PLoS Neglected Tropical Diseases |
| title | CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel. |
| title_full | CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel. |
| title_fullStr | CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel. |
| title_full_unstemmed | CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel. |
| title_short | CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel. |
| title_sort | cd4 cd25hifoxp3 regulatory t cells and cytokine responses in human schistosomiasis before and after treatment with praziquantel |
| url | http://europepmc.org/articles/PMC4546370?pdf=render |
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