Th2 cell-intrinsic hypo-responsiveness determines susceptibility to helminth infection.
The suppression of protective Type 2 immunity is a principal factor driving the chronicity of helminth infections, and has been attributed to a range of Th2 cell-extrinsic immune-regulators. However, the intrinsic fate of parasite-specific Th2 cells within a chronic immune down-regulatory environmen...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003215&type=printable |
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| author | Nienke van der Werf Stephen A Redpath Miyuki Azuma Hideo Yagita Matthew D Taylor |
| author_facet | Nienke van der Werf Stephen A Redpath Miyuki Azuma Hideo Yagita Matthew D Taylor |
| author_sort | Nienke van der Werf |
| collection | DOAJ |
| description | The suppression of protective Type 2 immunity is a principal factor driving the chronicity of helminth infections, and has been attributed to a range of Th2 cell-extrinsic immune-regulators. However, the intrinsic fate of parasite-specific Th2 cells within a chronic immune down-regulatory environment, and the resultant impact such fate changes may have on host resistance is unknown. We used IL-4gfp reporter mice to demonstrate that during chronic helminth infection with the filarial nematode Litomosoides sigmodontis, CD4(+) Th2 cells are conditioned towards an intrinsically hypo-responsive phenotype, characterised by a loss of functional ability to proliferate and produce the cytokines IL-4, IL-5 and IL-2. Th2 cell hypo-responsiveness was a key element determining susceptibility to L. sigmodontis infection, and could be reversed in vivo by blockade of PD-1 resulting in long-term recovery of Th2 cell functional quality and enhanced resistance. Contrasting with T cell dysfunction in Type 1 settings, the control of Th2 cell hypo-responsiveness by PD-1 was mediated through PD-L2, and not PD-L1. Thus, intrinsic changes in Th2 cell quality leading to a functionally hypo-responsive phenotype play a key role in determining susceptibility to filarial infection, and the therapeutic manipulation of Th2 cell-intrinsic quality provides a potential avenue for promoting resistance to helminths. |
| format | Article |
| id | doaj-art-1b1001b6fb684297b5e75eb982e7ecb6 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2013-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-1b1001b6fb684297b5e75eb982e7ecb62025-08-20T03:25:03ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-03-0193e100321510.1371/journal.ppat.1003215Th2 cell-intrinsic hypo-responsiveness determines susceptibility to helminth infection.Nienke van der WerfStephen A RedpathMiyuki AzumaHideo YagitaMatthew D TaylorThe suppression of protective Type 2 immunity is a principal factor driving the chronicity of helminth infections, and has been attributed to a range of Th2 cell-extrinsic immune-regulators. However, the intrinsic fate of parasite-specific Th2 cells within a chronic immune down-regulatory environment, and the resultant impact such fate changes may have on host resistance is unknown. We used IL-4gfp reporter mice to demonstrate that during chronic helminth infection with the filarial nematode Litomosoides sigmodontis, CD4(+) Th2 cells are conditioned towards an intrinsically hypo-responsive phenotype, characterised by a loss of functional ability to proliferate and produce the cytokines IL-4, IL-5 and IL-2. Th2 cell hypo-responsiveness was a key element determining susceptibility to L. sigmodontis infection, and could be reversed in vivo by blockade of PD-1 resulting in long-term recovery of Th2 cell functional quality and enhanced resistance. Contrasting with T cell dysfunction in Type 1 settings, the control of Th2 cell hypo-responsiveness by PD-1 was mediated through PD-L2, and not PD-L1. Thus, intrinsic changes in Th2 cell quality leading to a functionally hypo-responsive phenotype play a key role in determining susceptibility to filarial infection, and the therapeutic manipulation of Th2 cell-intrinsic quality provides a potential avenue for promoting resistance to helminths.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003215&type=printable |
| spellingShingle | Nienke van der Werf Stephen A Redpath Miyuki Azuma Hideo Yagita Matthew D Taylor Th2 cell-intrinsic hypo-responsiveness determines susceptibility to helminth infection. PLoS Pathogens |
| title | Th2 cell-intrinsic hypo-responsiveness determines susceptibility to helminth infection. |
| title_full | Th2 cell-intrinsic hypo-responsiveness determines susceptibility to helminth infection. |
| title_fullStr | Th2 cell-intrinsic hypo-responsiveness determines susceptibility to helminth infection. |
| title_full_unstemmed | Th2 cell-intrinsic hypo-responsiveness determines susceptibility to helminth infection. |
| title_short | Th2 cell-intrinsic hypo-responsiveness determines susceptibility to helminth infection. |
| title_sort | th2 cell intrinsic hypo responsiveness determines susceptibility to helminth infection |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003215&type=printable |
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