ArticlePLoS pathogens2013
Th2 cell-intrinsic hypo-responsiveness determines susceptibility to helminth infection.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
- T cell exhaustion in parasitic infections.Frontiers in immunology · 2026Review
- Helminths as architects of trained tolerance: implications for human health.Clinical & translational immunology · 2026Review
- PD-L2 Inhibits Protective Immunity, Th2 Cell Functional Quality, and GATA-3 Expression During Filarial Nematode Infection.European journal of immunology · 2025Article
- Successful management of chronic eosinophilic pneumonia triggered by immune checkpoint inhibitor: a case report and literature review.Frontiers in immunology · 2025Review
- Dysfunction of type 1 and type 2 immune cells: a lesson from exhausted-like ILC2s and their activation-induced cell death.International immunology · 2024Review
- Review of T Helper 2-Type Inflammatory Diseases Following Immune Checkpoint Inhibitor Treatment.Biomedicines · 2024Review
- Characterization of the immunosuppressive environment induced by larvalInfection and immunity · 2024Article
- M1/M2 macrophages and their overlaps - myth or reality?Clinical science (London, England : 1979) · 2023Article
- T helper 2 cells control monocyte to tissue-resident macrophage differentiation during nematode infection of the pleural cavity.Immunity · 2023Article
- NLRP3 Plays a Key Role in Antihelminth Immunity in the Enteral and Parenteral Stages of Trichinella spiralis-Infected Mice.Infection and immunity · 2023Article
- ILC2s Control Microfilaremia DuringFrontiers in immunology · 2022Article
- Human filariasis-contributions of the Litomosoides sigmodontis and Acanthocheilonema viteae animal model.Parasitology research · 2021Review
- Concurrent Infection With the Filarial HelminthFrontiers in immunology · 2021Article
- Filarial Lymphedema Patients Are Characterized by Exhausted CD4Frontiers in cellular and infection microbiology · 2021Article
- Case Report: A Squamous Cell Lung Carcinoma Patient Who Responded to Neoadjuvant Immunochemotherapy but Died From Anastomosis Leakage or/and irAEs: Immune Microenvironment and Genomic Features Changes.Frontiers in oncology · 2021Article
- The biomarkers related to immune related adverse events caused by immune checkpoint inhibitors.Journal of experimental & clinical cancer research : CR · 2020Review
- Systemic profile of immune factors in an elderly Italian population affected by chronic strongyloidiasis.Parasites & vectors · 2020Article
- The immune response of inbred laboratory mice to Litomosoides sigmodontis: A route to discovery in myeloid cell biology.Parasite immunology · 2020Review
- B cells induced by Schistosoma japonicum infection display diverse regulatory phenotypes and modulate CD4Parasites & vectors · 2020Article
- Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4)- and Programmed Death 1 (PD-1)-Mediated Regulation of Monofunctional and Dual Functional CD4Infection and immunity · 2019Article
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 4 countries.
Funding
Abstract
The suppression of protective Type 2 immunity is a principal factor driving the chronicity of helminth infections, and has been attributed to a range of Th2 cell-extrinsic immune-regulators. However, the intrinsic fate of parasite-specific Th2 cells within a chronic immune down-regulatory environment, and the resultant impact such fate changes may have on host resistance is unknown. We used IL-4gfp reporter mice to demonstrate that during chronic helminth infection with the filarial nematode Litomosoides sigmodontis, CD4(+) Th2 cells are conditioned towards an intrinsically hypo-responsive phenotype, characterised by a loss of functional ability to proliferate and produce the cytokines IL-4, IL-5 and IL-2. Th2 cell hypo-responsiveness was a key element determining susceptibility to L. sigmodontis infection, and could be reversed in vivo by blockade of PD-1 resulting in long-term recovery of Th2 cell functional quality and enhanced resistance. Contrasting with T cell dysfunction in Type 1 settings, the control of Th2 cell hypo-responsiveness by PD-1 was mediated through PD-L2, and not PD-L1. Thus, intrinsic changes in Th2 cell quality leading to a functionally hypo-responsive phenotype play a key role in determining susceptibility to filarial infection, and the therapeutic manipulation of Th2 cell-intrinsic quality provides a potential avenue for promoting resistance to helminths.
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