AITHM Seminar: Prof Rick Maizels and Dr Henry McSorley
Our work focuses on the excretory/secretory products of the murine intestinal parasite Heligmosomoides polygyrus, which contains several modulators of the host immune system. In mouse models of asthma, we found that H. polygyrus products suppressed the release of IL-33, inhibiting the development of type 2 immune responses. IL-33 is an “alarmin” cytokine released from necrotic epithelial cells, and is a potent activator of type 2 innate lymphoid cells, mast cells and Th2 cells. We subsequently identified a single protein from the parasite which mediates this effect, which we named the H. polygyrus Alarmin Release Inhibitor (HpARI). HpARI binds directly to IL-33, and to genomic DNA, tethering IL-33 to DNA within necrotic cells and preventing its release. Our subsequent work has focussed on further inhibitors of the pro-allergic epithelial cytokines IL-33, IL-25 and TSLP, which may act directly on these cytokines or their receptors.