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

Authors

Ivy K. Brown, National Jewish Health
Nathan Dyjack, National Jewish Health
Mindy M. Miller, National Jewish Health
Harsha Krovi, University of Colorado Anschutz Medical Campus
Cydney Rios, National Jewish Health
Rachel Woolaver, University of Colorado Anschutz Medical Campus
Laura Harmacek, National Jewish Health
Ting Hui Tu, National Jewish Health
Brian P. O’Connor, National Jewish Health
Thomas Danhorn, National Jewish Health
Brian Vestal, National Jewish Health
Laurent Gapin, University of Colorado Anschutz Medical Campus
Clemencia Pinilla, Florida International University
Max A. Seibold, National Jewish Health
James Scott-Browne, National Jewish Health
Radleigh G. Santos, National Jewish HealthFollow
R. Lee Reinhardt, Nova Southeastern University

Document Type

Article

Publication Date

6-1-2021

Publication Title

PLoS Pathogens

ISSN

15537366

Volume

17

Issue/No.

6

Abstract

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.

NSUWorks Citation

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.; and Lee Reinhardt, R., "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" (2021). Mathematics Faculty Articles. 335.
https://nsuworks.nova.edu/math_facarticles/335

ORCID ID

0000-0002-8194-5502

DOI

10.1371/journal.ppat.1009602