IL-33 facilitates rapid expulsion of the parasitic nematode Strongyloides ratti from the intestine via ILC2- and IL-9-driven mast cell activation

PLoS Pathog. 2020 Dec 22;16(12):e1009121. doi: 10.1371/journal.ppat.1009121. eCollection 2020 Dec.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Immunity, Innate / immunology
  • Interleukin-33 / immunology*
  • Interleukin-9 / immunology*
  • Intestinal Diseases, Parasitic / immunology*
  • Intestines / immunology
  • Intestines / parasitology
  • Lymphocytes / immunology*
  • Mast Cells / immunology*
  • Mice
  • Strongyloides ratti / immunology
  • Strongyloidiasis / immunology*

Substances

  • Interleukin-33
  • Interleukin-9