IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 1; pp. 282 - 287
• Main Authors: Hung, Li-Yin, Lewkowich, Ian P., Dawson, Lucas A., Downey, Jordan, Yang, Yanfen, Smith, Dirk E., Herbert, De'Broski R.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.01.2013; National Acad Sciences
• Subjects: Analysis of Variance; Animals; Basophils; Biological Sciences; Cytokines; Eosinophils; Eosinophils - immunology; Flow Cytometry; Gene expression; Glycoproteins; Hookworm Infections - immunology; Hormones, Ectopic - immunology; Immunity; Immunology; Infections; Interleukin-13 - immunology; Interleukin-33; Interleukins - deficiency; Interleukins - immunology; Lungs; Lymphocytes; Mast cells; Mice; Nippostrongylus - immunology; Parasites; Real-Time Polymerase Chain Reaction; Rodents; T lymphocytes; Th2 Cells - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1206587110

Parasitic helminths are a major cause of chronic human disease, affecting more than 3 billion people worldwide. Host protection against most parasitic helminths relies upon Type 2 cytokine production, but the mechanisms that regulate interleukin (IL) 4 and 13 production from CD4⁺ R helper 2 cells (TH2) and innate lymphoid type 2 cells (ILC2s) remain incompletely understood. The epithelial cell-derived cytokines IL-25 and IL-33 promote Type 2 responses, but the extent of functional redundancy between these cytokines is unclear and whether Type 2 memory relies upon either IL-25 or IL-33 is unknown. Herein, we demonstrate a pivotal role for IL-33 in driving primary and anamnestic immunity against the rodent hookworm Nippostrongylus brasiliensis. IL-33-def icient mice have a selective defect in ILC2-derived IL-13 during both primary and secondary challenge infections but generate stronger canonical CD4⁺ T helper 2 cells responses (IL-4, IgE, mast cells, and basophils) than WT controls. Lack of IL-13 production in IL-33-deficient mice impairs resistin-like molecule beta (RELMβ) expression and eosinophil recruitment, which are two mechanisms that eliminate N. brasiliensis parasites from infected hosts. Thus, IL-33 is requisite for IL-13 but not IL-4-driven Type 2 responses during hookworm infection.