Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire.
The CD4+ T cell response is critical to host protection against helminth infection. How this response varies across different hosts and tissues remains an important gap in our understanding. Using IL-4-reporter mice to identify responding CD4+ T cells to Nippostrongylus brasiliensis infection, T cel...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Language: | English |
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Public Library of Science (PLoS)
2021-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009602&type=printable |
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| author | Ivy K Brown Nathan Dyjack Mindy M Miller Harsha Krovi Cydney Rios Rachel Woolaver Laura Harmacek Ting-Hui Tu Brian P O'Connor Thomas Danhorn Brian Vestal Laurent Gapin Clemencia Pinilla Max A Seibold James Scott-Browne Radleigh G Santos R Lee Reinhardt |
| author_facet | Ivy K Brown Nathan Dyjack Mindy M Miller Harsha Krovi Cydney Rios Rachel Woolaver Laura Harmacek Ting-Hui Tu Brian P O'Connor Thomas Danhorn Brian Vestal Laurent Gapin Clemencia Pinilla Max A Seibold James Scott-Browne Radleigh G Santos R Lee Reinhardt |
| author_sort | Ivy K Brown |
| collection | DOAJ |
| description | The CD4+ T cell response is critical to host protection against helminth infection. How this response varies across different hosts and tissues remains an important gap in our understanding. Using IL-4-reporter mice to identify responding CD4+ T cells to Nippostrongylus brasiliensis infection, T cell receptor sequencing paired with novel clustering algorithms revealed a broadly reactive and clonally diverse CD4+ T cell response. While the most prevalent clones and clonotypes exhibited some tissue selectivity, most were observed to reside in both the lung and lung-draining lymph nodes. Antigen-reactivity of the broader repertoires was predicted to be shared across both tissues and individual mice. Transcriptome, trajectory, and chromatin accessibility analysis of lung and lymph-node repertoires revealed three unique but related populations of responding IL-4+ CD4+ T cells consistent with T follicular helper, T helper 2, and a transitional population sharing similarity with both populations. The shared antigen reactivity of lymph node and lung repertoires combined with the adoption of tissue-specific gene programs allows for the pairing of cellular and humoral responses critical to the orchestration of anti-helminth immunity. |
| format | Article |
| id | doaj-art-bfee9113d1934b3d8063baf5f57b2905 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2021-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-bfee9113d1934b3d8063baf5f57b29052025-08-20T02:54:33ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-06-01176e100960210.1371/journal.ppat.1009602Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire.Ivy K BrownNathan DyjackMindy M MillerHarsha KroviCydney RiosRachel WoolaverLaura HarmacekTing-Hui TuBrian P O'ConnorThomas DanhornBrian VestalLaurent GapinClemencia PinillaMax A SeiboldJames Scott-BrowneRadleigh G SantosR Lee ReinhardtThe CD4+ T cell response is critical to host protection against helminth infection. How this response varies across different hosts and tissues remains an important gap in our understanding. Using IL-4-reporter mice to identify responding CD4+ T cells to Nippostrongylus brasiliensis infection, T cell receptor sequencing paired with novel clustering algorithms revealed a broadly reactive and clonally diverse CD4+ T cell response. While the most prevalent clones and clonotypes exhibited some tissue selectivity, most were observed to reside in both the lung and lung-draining lymph nodes. Antigen-reactivity of the broader repertoires was predicted to be shared across both tissues and individual mice. Transcriptome, trajectory, and chromatin accessibility analysis of lung and lymph-node repertoires revealed three unique but related populations of responding IL-4+ CD4+ T cells consistent with T follicular helper, T helper 2, and a transitional population sharing similarity with both populations. The shared antigen reactivity of lymph node and lung repertoires combined with the adoption of tissue-specific gene programs allows for the pairing of cellular and humoral responses critical to the orchestration of anti-helminth immunity.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009602&type=printable |
| spellingShingle | Ivy K Brown Nathan Dyjack Mindy M Miller Harsha Krovi Cydney Rios Rachel Woolaver Laura Harmacek Ting-Hui Tu Brian P O'Connor Thomas Danhorn Brian Vestal Laurent Gapin Clemencia Pinilla Max A Seibold James Scott-Browne Radleigh G Santos R Lee Reinhardt Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire. PLoS Pathogens |
| title | Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire. |
| title_full | Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire. |
| title_fullStr | Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire. |
| title_full_unstemmed | Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire. |
| title_short | Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire. |
| title_sort | single cell analysis of host response to helminth infection reveals the clonal breadth heterogeneity and tissue specific programming of the responding cd4 t cell repertoire |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009602&type=printable |
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