In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 7 ( 2021-7-8), p. e1009709-
Abstract:
Helminths are distinct from microbial pathogens in both size and complexity, and are the likely evolutionary driving force for type 2 immunity. CD4+ helper T cells can both coordinate worm clearance and prevent immunopathology, but issues of T cell antigen specificity in the context of helminth-induced Th2 and T regulatory cell (Treg) responses have not been addressed. Herein, we generated a novel transgenic line of the gastrointestinal nematode Strongyloides ratti expressing the immunodominant CD4+ T cell epitope 2W1S as a fusion protein with green fluorescent protein (GFP) and FLAG peptide in order to track and study helminth-specific CD4+ T cells. C57BL/6 mice infected with this stable transgenic line (termed Hulk ) underwent a dose-dependent expansion of activated CD44 hi CD11a hi 2W1S-specific CD4+ T cells, preferentially in the lung parenchyma. Transcriptional profiling of 2W1S-specific CD4+ T cells isolated from mice infected with either Hulk or the enteric bacterial pathogen Salmonella expressing 2W1S revealed that pathogen context exerted a dominant influence over CD4+ T cell phenotype. Interestingly, Hulk -elicited 2W1S-specific CD4+ T cells exhibited both Th2 and Treg phenotypes and expressed high levels of the EGFR ligand amphiregulin, which differed greatly from the phenotype of 2W1S-specific CD4+ T cells elicited by 2W1S-expressing Salmonella . While immunization with 2W1S peptide did not enhance clearance of Hulk infection, immunization did increase total amphiregulin production as well as the number of amphiregulin-expressing CD3+ cells in the lung following Hulk infection. Altogether, this new model system elucidates effector as well as immunosuppressive and wound reparative roles of helminth-specific CD4+ T cells. This report establishes a new resource for studying the nature and function of helminth-specific T cells.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009709
DOI:
10.1371/journal.ppat.1009709.g001
DOI:
10.1371/journal.ppat.1009709.g002
DOI:
10.1371/journal.ppat.1009709.g003
DOI:
10.1371/journal.ppat.1009709.g004
DOI:
10.1371/journal.ppat.1009709.g005
DOI:
10.1371/journal.ppat.1009709.g006
DOI:
10.1371/journal.ppat.1009709.s001
DOI:
10.1371/journal.ppat.1009709.s002
DOI:
10.1371/journal.ppat.1009709.s003
DOI:
10.1371/journal.ppat.1009709.s004
DOI:
10.1371/journal.ppat.1009709.s005
DOI:
10.1371/journal.ppat.1009709.s006
DOI:
10.1371/journal.ppat.1009709.s007
DOI:
10.1371/journal.ppat.1009709.s008
DOI:
10.1371/journal.ppat.1009709.s009
DOI:
10.1371/journal.ppat.1009709.s010
DOI:
10.1371/journal.ppat.1009709.s011
DOI:
10.1371/journal.ppat.1009709.s012
DOI:
10.1371/journal.ppat.1009709.r001
DOI:
10.1371/journal.ppat.1009709.r002
DOI:
10.1371/journal.ppat.1009709.r003
DOI:
10.1371/journal.ppat.1009709.r004
DOI:
10.1371/journal.ppat.1009709.r005
DOI:
10.1371/journal.ppat.1009709.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1