IL-33 is essential to prevent high-fat diet-induced obesity in mice infected with an intestinal helminth

Parasite Immunol. 2020 Sep;42(9):e12700. doi: 10.1111/pim.12700. Epub 2020 Jun 16.


Intestinal helminthes induce immunosuppressive responses as well as type 2 immunity. Their suppressive properties are intended to regulate inflammatory diseases such as allergies and autoimmune diseases. This study evaluated whether helminthic infections suppress obesity, a chronic inflammatory state, using an intestinal nematode, Heligmosomoides polygyrus (Hp). Infection with Hp at the same time as feeding a high-fat diet (HFD) prevented weight gain, dyslipidaemia and glucose intolerance observed in uninfected obese mice. Immunologically, Hp infection skewed M1 macrophages to M2 macrophages and induced type 2 innate lymphoid cells in adipose tissues. The expression of interleukin (IL)-33, a potent initiator of type 2 responses, was also increased in association with uncoupled protein 1 (UCP1). To further investigate the anti-obesity effects of IL-33 in mice infected with Hp, IL-33-deficient mice were fed the HFD and infected with Hp. These mutant mice rapidly gained weight compared with wild-type mice, indicating the anti-obesity effect of IL-33. In the absence of IL-33, the rapid increase in weight was not prevented, and type 2 responses and UCP1 expression were not observed even during Hp infection. These results suggested that the suppression of obesity by Hp is dependent on IL-33.

Keywords: adipokines; hygiene hypothesis; immune regulation; parasitic nematodes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / immunology
  • Animals
  • Diet, High-Fat*
  • Immunity, Innate
  • Interleukin-33 / physiology*
  • Intestinal Diseases, Parasitic / complications
  • Intestinal Diseases, Parasitic / immunology*
  • Lymphocytes / immunology
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nematospiroides dubius* / immunology
  • Obesity / immunology
  • Obesity / prevention & control*
  • Strongylida Infections / immunology*
  • Therapy with Helminths


  • Il33 protein, mouse
  • Interleukin-33