ArticleMucosal immunology2016
Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths.
Article in Mucosal immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
51 citing papers in PubMed, 74 citations in OpenAlex.
- From infection to cholangiocarcinoma: Why opisthorchiids break these rules.One health (Amsterdam, Netherlands) · 2026Review
- Metabolic sensor AMPK licenses intestinal CD103Science advances · 2026Article
- Molecular Engineering of the Helminth TGF-β Mimetics, TGM1 and TGM4, Reveals a Novel Antagonist of TGF-β Signaling in Fibroblasts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Heligmosomid infections in bank voles are associated with higher prevalence and greater abundance of other helminth species.Parasitology · 2026Article
- Differential generation of parasite-specific Th2 and T follicular helper cells distinguishes resistant and susceptible mouse strains.Frontiers in immunology · 2026Article
- Entamoeba muris provides a mouse model for amoebic colitis pathology characterized by T cell associated colonization.Scientific reports · 2025Article
- Cytokines from parasites: manipulating host responses by molecular mimicry.The Biochemical journal · 2025Review
- TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts.Nature communications · 2025Article
- Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homing.Scientific reports · 2025Article
- Immunological feedback loops generate parasite persistence thresholds that explain variation in infection duration.Proceedings. Biological sciences · 2024Article
- Controlled human hookworm infection remodels plasmacytoid dendritic cells and regulatory T cells towards profiles seen in natural infections in endemic areas.Nature communications · 2024Article
- Systemic Immune Modulation by Gastrointestinal Nematodes.Annual review of immunology · 2024Review
- IL-33-binding HpARI family homologues with divergent effects in suppressing or enhancing type 2 immune responses.Infection and immunity · 2024Article
- Article
- Adaptive plasticity of natural interleukin-35-induced regulatory T cells (Tr35) that are required for T-cell immune regulation.Theranostics · 2024Article
- Targeting helminths: The expanding world of type 2 immune effector mechanisms.The Journal of experimental medicine · 2023Review
- Convergent Evolution in a Murine Intestinal Parasite Rapidly Created the TGM Family of Molecular Mimics to Suppress the Host Immune Response.Genome biology and evolution · 2023Review
- Intestinal Helminth Infection Impairs Oral and Parenteral Vaccine Efficacy.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Convergent evolution of a parasite-encoded complement control protein-scaffold to mimic binding of mammalian TGF-β to its receptors, TβRI and TβRII.The Journal of biological chemistry · 2022Article
- Age-dependent rise in IFN-γ competence undermines effective type 2 responses to nematode infection.Mucosal immunology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.