IL-33 facilitates rapid expulsion of the parasitic nematode Strongyloides ratti from the intestine via ILC2- and IL-9-driven mast cell activation |
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| Authors: | Jana Meiners Martina Reitz Nikolas Rüdiger Jan-Eric Turner Lennart Heepmann Lena Rudolf Wiebke Hartmann Henry J McSorley Minka Breloer |
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| Institution: | 1. Bernhard Nocht Institute for Tropical Medicine, Section of Molecular Biology and Immunology, Hamburg, Germany;2. III. Department of Medicine and Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;3. Division of Cell signaling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom;4. Department of Biology, University of Hamburg, Hamburg, Germany;University of California Riverside, UNITED STATES |
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| Abstract: | Parasitic helminths are sensed by the immune system via tissue-derived alarmins that promote the initiation of the appropriate type 2 immune responses. Here we establish the nuclear alarmin cytokine IL-33 as a non-redundant trigger of specifically IL-9-driven and mast cell-mediated immunity to the intestinal parasite Strongyloides ratti. Blockade of endogenous IL-33 using a helminth-derived IL-33 inhibitor elevated intestinal parasite burdens in the context of reduced mast cell activation while stabilization of endogenous IL-33 or application of recombinant IL-33 reciprocally reduced intestinal parasite burdens and increased mast cell activation. Using gene-deficient mice, we show that application of IL-33 triggered rapid mast cell-mediated expulsion of parasites directly in the intestine, independent of the adaptive immune system, basophils, eosinophils or Gr-1+ cells but dependent on functional IL-9 receptor and innate lymphoid cells (ILC). Thereby we connect the described axis of IL-33-mediated ILC2 expansion to the rapid initiation of IL-9-mediated and mast cell-driven intestinal anti-helminth immunity. |
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