Nematode ascarosides attenuate mammalian type 2 inflammatory responses

Abstract

Significance Animal proof-of-concept studies have shown that roundworms have a protective effect against immune-dysregulated disorders, but it has been difficult to study in human trials without individual nematode-derived molecules to develop and test. We discovered that ascarosides, molecules that are secreted by diverse nematodes, suppress asthma in a rodent model via modulation of expression of Il33 , a key epithelial cytokine for induction of type 2 immunity, in addition to decreasing memory-type pathogenic Th2 cells and ILC2s and increasing the Il10- expressing subpopulation of interstitial macrophages in the lung. Thus, ascarosides suppress type 2 immune response by affecting both innate and adaptive immunity and could define a potent class of small molecule drugs to treat allergic airway diseases.