Dr Henry McSorley
Henry McSorley's research focuses on identifying and characterising immunomodulatory molecules from parasitic helminth secretions, and investigating their therapeutic potential in immune-mediated diseases such as asthma.
- Caroline Chauche - Postdoctoral researcher
- Francesco Vacca - PhD student
- Piotr Janas - MSc student
- Megan Osbourn (now a core lab technologist at Almac diagnostics, Belfast)
- Dinesh Soares (now managing editor at ACS Omega journal)
Many studies have shown that immune-mediated diseases such as asthma, Inflammatory Bowel Disease (IBD) and autoimmunity are less common in parasite-endemic populations than in the developed world, where parasitic infection is rare. This led to the hypothesis that parasitic worms secrete immunomodulatory molecules which prevent the development of inappropriate immune responses. Animal model studies have confirmed that parasitic infection, or the administration of parasite secretions, suppresses inflammatory immune responses. As genomic information about helminth parasites is becoming available, we are now able to mine the parasite secretome for defined immunomodulators which could be developed as therapeutic agents in human disease.
Our focus if on the immunomodulatory activities of helminth parasites, and how these could be developed as therapeutic agents in human immune-mediated diseases. Parasitic helminths have developed a range of sophisticated techniques for modulation of the host immune response: this prevents ejection, causing minimal damage to both parasite and host. We believe they achieve this remarkable manipulation of the immune system through release of soluble immunomodulatory factors. Our hope is that by identifying and characterising these, we may learn how to better control immune responses, and develop parasite-derived factors as new therapeutic agents in human disease.
We identified the HpARI protein from the murine intestinal parasite Heligmosomoides polygyrus. HpARI binds to IL-33, tethering it within necrotic cells and inhibiting binding of IL-33 to its receptor. IL-33 is strongly implicated in the development of allergy, and administration of HpARI potently suppresses inflammation in models of asthma. Furthermore, HpARI is active against human IL-33 and thus has potential for direct development as a therapeutic agent in human IL-33-mediated allergic diseases (Osbourn, 2017, Immunity).
We are characterising the mechanism of action of HpARI, and other parasite-derived proteins, in modulation of the host immune response. We use models of parasitic and viral infection and immune-mediated diseases such as asthma in vivo and in vitro. We investigate mechanistic hypotheses in animal models, but aim to always translate our results to human disease.
Sources of Funding
- 01/2018 – 12/2019: Dutch Lung Foundation (Longfonds) International Consortium Grant (€160,000). “A World Without Asthma”. Role: Co-I
- 08/2016 – 08/2017: Medical Research Council Confidence in Concept Scheme (£94,753.20). “Novel therapeutics for suppression of IL-33 in severe allergic asthma”. Role: PI
- 05/2016 – 05/2017: Wellcome Trust International Strategic Support Fund (£27,962). “Suppressing the IL-33 pathway in RSV-induced airway allergy”. Role: PI
- 05/2014 – 05/2019: Chancellor’s Fellowship (£30,000). Startup funds and a PhD studentship. Role: PI
- 07/2013 – 09/2016: Asthma UK Senior Postdoctoral Fellowship (£224,672). “How do parasite products modulate the early events in allergic responses?”. Role: PI
Osbourn M*, Soares DC*, Vacca F*, Cohen ES, Scott IC, Gregory WF, Smyth DJ, Toivakka M, Kemter AM, le Bihan T, Wear M, Hoving D, Filbey KJ, Hewitson JP, Henderson H, Gonzàlez A, Errington C, Vermeren S, Astier AL, Wallace WA, Schwarze J, Ivens AC, Maizels RM**, McSorley HJ**. (2017) A Helminth-derived Inhibitor of Interleukin-33. Immunity. 47:739.
Pastille E, Frede A, McSorley HJ, Gräb J, Adamczyk A, Kollenda S, Hansen W, Epple M, Buer J, Maizels RM, Klopfleisch R, Westendorf AM. (2017) Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer. PLoS Pathog. 13:e1006649.
Kerrin A, Fitch P, Errington C, Kerr D, Waxman L, Riding K, McCormack J, Mehendele F, McSorley H, MacKenzie K, Wronski S, Braun A, Levin R, Theilen U, Schwarze J. (2017) Differential lower airway dendritic cell patterns may reveal distinct endotypes of RSV bronchiolitis. Thorax. 72:620-627.
Robb CT, McSorley HJ, Lee J, Aoki T, Yu C, Crittenden S, Astier A, Felton JM, Parkinson N, Ayele A, Breyer RM, Anderton SM, Narumiya S, Rossi AG, Howie SE, Guttman-Yassky E, Weller RB, Yao C. (2017) Prostaglandin E2 stimulates adaptive IL-22 production and promotes allergic contact dermatitis. J Allergy Clin Immunol. pii: S0091-6749(17)30914-
Coakley G, McCaskill JL, Borger JG, Simbari F, Robertson E, Millar M, Harcus Y, McSorley HJ, Maizels RM, Buck AH. (2017) Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity. Cell Rep. 19(8):1545-1557.
McFarlane AJ, McSorley HJ, Davidson DJ, Fitch PM, Errington C, Mackenzie KJ, Gollwitzer ES, Johnston CJ, MacDonald AS, Edwards MR, Harris NL, Marsland BJ, Maizels RM, Schwarze J. (2017) Enteric helminth-induced type I interferon signaling protects against pulmonary virus infection through interaction with the microbiota. J Allergy Clin Immunol. pii: S0091-6749(17)30229-4.
Maizels RM, McSorley HJ. (2016) Regulation of the host immune system by helminth parasites. J Allergy Clin Immunol. 138(3):666-75.
Jackson-Jones LH, Duncan SM, Magalhaes MS, Campbell SM, Maizels RM, McSorley HJ, Allen JE, Bénézech C. (2016) Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation. Nat Commun. 7:12651
Smits HH, Hiemstra PS, Prazeres da Costa C, Ege M, Edwards M, Garn H, Howarth PH, Jartti T, de Jong EC, Maizels RM, Marsland BJ, McSorley HJ, Müller A, Pfefferle PI, Savelkoul H, Schwarze J, Unger WW, von Mutius E, Yazdanbakhsh M, Taube C. (2016) Microbes and asthma: Opportunities for intervention. J Allergy Clin Immunol. 137(3):690
McSorley HJ, Blair NF, Robertson E, Maizels RM. (2015) Suppression of OVA-alum induced allergy by Heligmosomoides polygyrus products is MyD88-, TRIF-, regulatory T- and B cell-independent, but is associated with reduced innate lymphoid cell activation. Exp Parasitol. 158:8
Buck AH, Coakley G, Simbari F, McSorley HJ, Quintana JF, Le Bihan T, Kumar S, Abreu-Goodger C, Lear M, Harcus Y, Ceroni A, Babayan SA, Blaxter M, Ivens A, Maizels RM. (2014) Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nat Commun. 25;5:5488.
McSorley HJ, Blair NF, Smith KA, McKenzie ANJ, Maizels RM. (2014) Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy. Mucosal Immunol. 7(5):1068.
Hewitson JP, Ivens AC, Harcus Y, Filbey KJ, McSorley HJ, Murray J, Bridgett S, Ashford D, Dowle AA, Maizels RM. (2013) Secretion of protective antigens by tissue-stage nematode larvae revealed by proteomic analysis and vaccination-induced sterile immunity. PLoS Pathog. 9(8):e1003492.
Ferreira I, Smyth D, Gaze S, Aziz A, Giacomin P, Ruyssers N, Artis D, Laha T, Navarro S, Loukas A*, McSorley HJ*. (2013) Hookworm excretory/secretory products induce interleukin-4 (IL-4)+ IL-10+ CD4+ T cell responses and suppress pathology in a mouse model of colitis. Infect Immun. 81(6):2104-11.
McSorley HJ, Maizels RM. (2012) Helminth infections and host immune regulation. Clin Microbiol Rev. 25(4):585-608.
McSorley HJ*, O'Gorman MT*, Blair N, Sutherland TE, Filbey KJ, Maizels RM. (2012) Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus. Eur J Immunol. 42(10):2667-82
Gaze S*, McSorley HJ*, Daveson J, Jones D, Bethony JM, Oliveira LM, Speare R, McCarthy JS, Engwerda CR, Croese J, Loukas A. (2012) Characterising the mucosal and systemic immune responses to experimental human hookworm infection. PLoS Pathog. 8(2):e1002520.
McSorley HJ*, Gaze S*, Daveson J, Jones D, Anderson RP, Clouston A, Ruyssers NE, Speare R, McCarthy JS, Engwerda CR, Croese J, Loukas A. (2011) Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection. PLoS One. 6(9):e24092
Grainger JR, Smith KA, Hewitson JP, McSorley HJ, Harcus Y, Filbey KJ, Finney CA, Greenwood EJ, Knox DP, Wilson MS, Belkaid Y, Rudensky AY, Maizels RM (2010) Helminth secretions induce de novo Foxp3 expression and regulatory function through the TGF-beta pathway. J Exp Med, 207:2331-2341
McSorley HJ, Harcus YM, Murray J, Taylor MD, Maizels RM. (2008) Expansion of Foxp3+ regulatory T cells in mice infected with the filarial parasite Brugia malayi. J Immunol. 181:6456-66.