Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4.sup.+ T cell repertoire

The CD4.sup.+ 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.sup.+ T cells to Nippostrongylus brasiliensis infect...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2021-06, Vol.17 (6)
Main Authors: Brown, Ivy K, Dyjack, Nathan, Miller, Mindy M, Krovi, Harsha, Rios, Cydney, Woolaver, Rachel, Harmacek, Laura, Tu, Ting-Hui, O'Connor, Brian P, Danhorn, Thomas, Vestal, Brian, Gapin, Laurent, Pinilla, Clemencia, Seibold, Max A, Scott-Browne, James, Santos, Radleigh G, Reinhardt, R. Lee
Format: Article
Language:English
Subjects:
Antigen-antibody reactions
CD4 lymphocytes
Development and progression
Health aspects
Helminthiasis
Host-parasite relationships
Parasitological research
Physiological aspects
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The CD4.sup.+ 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.sup.+ T cells to Nippostrongylus brasiliensis infection, T cell receptor sequencing paired with novel clustering algorithms revealed a broadly reactive and clonally diverse CD4.sup.+ 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.sup.+ CD4.sup.+ 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.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1009602