Helminth-Induced Modulation of Host Immune Responses

Helminth parasites have co-evolved with vertebrate hosts to establish long-term infections by orchestrating profound changes in immune function. They characteristically induce a Th2-polarised response, marked by interleukins IL-4, IL-5 and IL-13, while promoting regulatory networks such as Foxp3+ regulatory T cells and alternatively activated macrophages. These effects are mediated by a suite of excretory/secretory molecules, including protease inhibitors, lipid-binding proteins and cytokine mimics, which disrupt antigen presentation, cytokine signalling pathways and host metabolic routes. The net result is attenuation of inflammatory and allergic reactions, modulation of vaccine responsiveness and potential impacts on co-infection dynamics. Insight into these mechanisms offers avenues for novel immunotherapies, vaccine adjuvants and strategies to manage inflammatory disorders in endemic settings.

Research from Nature Portfolio

Recent studies have identified a parasite-derived transforming growth factor-β mimic that binds host TGF-β receptors, driving expansion of Foxp3+ regulatory T cells in both murine and human systems. This finding reveals a sophisticated example of convergent evolution in immune modulation and pinpoints a molecular lead for designing helminth-inspired therapeutics to treat autoimmune and inflammatory diseases.

Helminth-Induced Modulation of Host Immune Responses publication trend

The graph below shows the total number of articles in helminth-induced modulation of host immune responses across all publications each year (not limited to Nature Index journals).

Technical terms

Excretory/secretory (E/S) products: Molecules released by helminths that interact with host cells to modulate immune functions.

Regulatory T cells (Tregs): A subset of CD4+ T lymphocytes that suppress immune responses and maintain self-tolerance.

Transforming growth factor-β (TGF-β) mimic: A parasite-derived protein that engages host TGF-β receptors to trigger regulatory signalling pathways.

Mevalonate pathway: A metabolic cascade in host cells leading to cholesterol synthesis, targeted by certain helminth molecules.

Cytokine storm: An excessive and dysregulated release of proinflammatory cytokines causing tissue damage and organ dysfunction.

References

1. Regulation of the host immune system by helminth parasites. Journal of Allergy and Clinical Immunology (2016).
2. Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules. Immunity (2018).
3. A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells. Nature Communications (2017).
4. Controlled infection with cryopreserved human hookworm induces CTLA-4 expression on Tregs and upregulates tryptophan metabolism. Gut Microbes (2024).
5. Cystatin from the helminth Ascaris lumbricoides upregulates mevalonate and cholesterol biosynthesis pathways and immunomodulatory genes in human monocyte-derived dendritic cells. Frontiers in Immunology (2024).
6. IL-9 plays a critical role in helminth-induced protection against COVID-19-related cytokine storms. mBio (2024).