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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.
- Source :
- PLoS Pathogens; 6/9/2021, Vol. 17 Issue 6, p1-34, 34p
- Publication Year :
- 2021
-
Abstract
- The CD4<superscript>+</superscript> 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<superscript>+</superscript> T cells to Nippostrongylus brasiliensis infection, T cell receptor sequencing paired with novel clustering algorithms revealed a broadly reactive and clonally diverse CD4<superscript>+</superscript> 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<superscript>+</superscript> CD4<superscript>+</superscript> 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. Author summary: Using various "omic" approaches, the CD4<superscript>+</superscript> T cell receptor (TCR) repertoire was explored after primary helminth infection. Infection generated a broadly reactive and clonally diverse CD4<superscript>+</superscript> T cell response with the most prevalent clonotypes and predicted antigen specificities residing in both the lung and lung-draining lymph nodes. Tissue-specific programming of responding CD4<superscript>+</superscript> T cells directed the establishment of committed Tfh and Th2 cells, both critical for driving distinct hallmarks of type-2 inflammation. These datasets help to explore the diverse yet tissue-specific nature of anti-helminth immunity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 17
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 150797632
- Full Text :
- https://doi.org/10.1371/journal.ppat.1009602