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.
Regulation and Immunity in Helminth Infection
Presented by Prof. Rick Maizels
Professor Rick Maizels is at the Wellcome Centre for Integrative Parasitology in the University of Glasgow's Institute of Infection, Immunity and Inflammation. He is an immunologist interested in fundamental questions of how parasites suppress the mammalian immune system, primarily for their own survival but in so doing, also dampen allergies and other inflammatory disorders. His work aims to discover novel immunomodulators from parasites that may be useful in suppressing inflammation and disease, and to develop new vaccine strategies that can lead to clearance of these very prevalent parasites. His laboratory is supported by the Wellcome Trust, the Kenneth Rainin Foundation and the Lung Foundation Netherlands. Rick moved to the University of Glasgow in 2016; between 1995 and 2015 he held the Chair of Zoology at the University of Edinburgh, and was previously Professor of Parasite Immunology at Imperial College London, where he moved in 1983. Prior to this, he held positions at the National Institute for Medical Research in London (1973-1976 and 1979-1983), as well as UCLA (1977-1979) and California Institute of Technology (1986-1977). He was elected Fellow of the Royal Society of Edinburgh in 2002, a Senior Fellow of the American Asthma Foundation in 2010, and a Fellow of the Academy of Medical Sciences in 2018.
Contact details: Rick.Maizels@Glasgow.ac.uk
Helminth-derived inhibitors of early innate immune responses
Presented by Dr Henry McSorley
Dr McSorley graduated from the University of Glasgow in 2004 with an MSci in Immunology, and carried out my PhD in the lab of Rick Maizels at the University of Edinburgh (2004-2008). After postdocs with Alex Loukas at QIMR Berghofer and James Cook University Cairns (2008-2010) and Rick Maizels, Edinburgh (2010-2014), I received a postdoctoral Fellowship from Asthma UK (2013-2017) and then an independent Chancellor’s Fellowship from the University of Edinburgh (2014-2019).
Contact details: Henry.McSorley@ed.ac.uk