Type 2 Immune Responses in Helminth Infections

Type 2 immunity constitutes a specialised arm of the immune system that orchestrates defence against multicellular parasites such as helminths while also promoting tissue repair. Central to this response are cytokines interleukin-4, interleukin-5 and interleukin-13, which drive differentiation of T helper 2 (Th2) cells, activate alternatively-activated (M2) macrophages and recruit eosinophils and mast cells. Group 2 innate lymphoid cells (ILC2s) serve as rapid sources of type 2 cytokines at barrier surfaces, responding to epithelial alarmins such as interleukin-33. Together, innate and adaptive type 2 effectors expel intestinal and tissue-migrating worms by enhancing smooth-muscle contractility, mucus production and antibody-mediated cytotoxicity. Concurrently, they limit collateral damage through fibrosis, extracellular-matrix remodelling and resolution of inflammation. Helminth infections therefore represent a dynamic interplay between parasite clearance and wound repair, with global relevance for endemic regions and emerging immunotherapies against allergy and autoimmunity.

Research from Nature Portfolio

Recent studies have illuminated non-redundant roles for ILC2s in coordinating humoral immunity at barrier sites. One investigation demonstrated that ILC2-derived interleukin-5 is essential for the development and function of B1 cells, revealing that loss of IL-5 from ILC2s impairs natural antibody production against phosphatidylcholine antigens. This finding underscores a critical link between innate lymphoid sources of type 2 cytokines and T-independent B-cell responses. Foundational work has also characterised cooperative interactions between ILC2s and CD4+ T cells in the lung. In this model, ILC2s and Th2 cells sustain each other via interleukin-2 and interleukin-33-driven circuits, ensuring persistent activation of M2 macrophages that mediate larval killing of tissue-migrating hookworms. Such synergy highlights the importance of cross-talk between innate and adaptive components of type 2 immunity.

Type 2 Immune Responses in Helminth Infections publication trend

The graph below shows the total number of articles in type 2 immune responses in helminth infections across all publications each year (not limited to Nature Index journals).

Technical terms

Type 2 immune response: An immune programme driven by IL-4, IL-5 and IL-13 that targets multicellular parasites and mediates tissue repair.

ILC2 (Group 2 innate lymphoid cell): A tissue-resident innate lymphoid cell that produces type 2 cytokines in response to epithelial alarmins.

Th2 cell (T helper 2 cell): An adaptive CD4+ T cell subset that secretes IL-4, IL-5 and IL-13 to coordinate type 2 immunity.

Alternatively-activated (M2) macrophage: A macrophage phenotype induced by IL-4/IL-13 that supports parasite clearance, fibrosis regulation and tissue repair.

Alarmin: A host-derived signal (for example IL-33) released upon tissue injury that activates innate immune responses.

References

1. Group 2 innate lymphoid cells are a non-redundant source of interleukin-5 required for development and function of murine B1 cells. Nature Communications (2024).
2. ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms. Nature Communications (2015).
3. Targeting helminths: The expanding world of type 2 immune effector mechanisms. Journal of Experimental Medicine (2023).
4. IL-4 and IL-13: Regulators and Effectors of Wound Repair. Annual Review of Immunology (2023).
5. The IL-17A-neutrophil axis promotes epithelial cell IL-33 production during nematode lung migration. Mucosal Immunology (2023).