Dr William Horsnell

William Horsnell

Institute of Microbiology and Infection
Reader in Immunity to Infection

Contact details

Email
w.horsnell@bham.ac.uk
View my research portal
Address
Institute of Microbiology and Infection
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

William Horsnell is an immunologist focusing primarily on how helminth infections alter host immunity. He looks at how helminth elicited host responses influence host ability to control both the helminth infection and unrelated diseases. He studies these effects both using both model infections and also in human studies. Dr Horsnell is based at both the Universities of Birmingham and Cape Town.

Qualifications

  • PhD in Cell Biology, Royal Veterinary College, London 2001
  • BSc (Hons) Applied Zoology, University of Leeds 1996

Biography

Horsnell studies host immunity to helminths as these infections are very common and exert a profound influence on our immune system. Helminth infections lead to both transient and long lasting changes to host immunity. These effects on our immune system are important and influence how we can control both the helminth and unrelated infections. Horsnell is particularly interested in how helminths regulate host immunity by modulating a number of anti-helminth components released by the host.

In addition he looks at how exposure to both host adapted and zoonotic helminth infection change host susceptibility to a number of other diseases. These include respiratory syncytial virus, salmonella, tuberculosis and allergy. We also study the effects of helminth infection on both parasite colonised anatomical sites e.g. the intestine and lung as well as systemic effects at body sites the parasite does not colonise.

Our work utilises both basic animal models of disease as well as human studies. 

Research

Themes

Regulation of Host immunity by helminths, pulmonary immunity, neurotransmitter regulation of immunity.

Lay Summary

My research aims to identify how we launch immune response to control parasitic worm infections and how parasitic worms have adapted to influence this immunity. This approach has resulted in my team identifying novel mediators of protective immunity against these parasites and also to shed new understanding as to how these parasitic infections can change our immunity to other infections. Additionally, this work allows us to further understand how parasites regulate our immunity and if this regulation can be utilised for treating immune related pathologies, especially in the lung. 

Overview

Our principle approach is to use in vivo models of helminth infection to dissect how these parasites are controlled by a host and  how these host responses to the helminth influence the development of immune responses to other pathogens/diseases. We utilise primary, secondary and trans-generational models of helminth infection to identify how these different modes of exposure to helminths influence host control of infection. Moreover, we utilise existing and generate novel transgenic mouse models to test the significance of host molecular correlates of immunity to the helminths. We also examine how these different modes of exposure change host ability to launch immune responses to unrelated bacterial, viral, fungal infections as well as non-infectious diseases. These approaches have led to us identifying how non-canonical host responses to infection significantly contribute to immunity to helminths. The hypotheses generated from these studies are then tested in appropriate human cohort studies.

Ongoing research themes

  1. Host immunity to primary, secondary and maternal exposure to the model parasitic helminth Nippostrongylus brasiliiensis.
  2. How helminth infections alter immunity to viral infection of mucosal tissue.
  3. Influence of helminth infection on the onset of mycobacterial infection and disease in mice and humans
  4. Helminth exposure and risk of allergy in humans in Northern Europe and Southern Africa
  5. Role of Surfactant Proteins A and D in immunity to parasitic and viral infections.
  6. Generating novel transgenic mouse models to define the significance of immune cell production and responsiveness to acetylcholine

Other activities

  • Reviewer for a number of high-impact, internationally-competitive, journals and international funding agencies
  • Organized a number of national and international meetings on infection and immunology
  • Scientific Advisory Board: RHINESSA: http://www.uib.no/node/91891
  • Treasurer South African Immunology Society 2011-2018

Publications

Patents

Submitted:

  1. Horsnell WG & Clark HW. Protection against parasitic nematode infection by surfactant (SP-D) - RIS 13458. UK Patent Application No 1402909.4 University of Southampton AND University of Cape Town Filed 19th February 2014

Publications

 (*: Equal contributions to publication. #: Corresponding authors):

Research papers:

1. Hoving C, Cutler A, Leeto M, Horsnell WG, Dewals B, Niewenhuizen N, Brombacher F. Interleukin-13-mediated colitis in the absence of IL-4Rα signalling. Gut. 2017 Feb 28. pii:. (IF: 14.921)

2. Thawer S*, Auret J*, Schnoeller C, Chetty A, Smith KA, Darby M, Roberts L, Mackay RM, Whitwell HJ, Timms JF, Madsen J, Selkirk ME, Brombacher F, Clark HW#, Horsnell WG#. Surfactant Protein-D is essential for immunity to helminth infection.PLoS Pathogens 2016. Feb 22. 12 (2): e1005461. (IF: 8.136)

3. Kirstein F,  Nieuwenhuizen N, Jayakumar J, Horsnell WG,  Brombacher F. Role of IL-4Ra+CD4+ T cells in chronic airway hyper-responsiveness. .Journal of Allergy and Clinical Immunology 2016 Dec 11. pii: S0091-6749(15)01670-X. (IF 12.047)

4. Darby M*, Schnoeller C*, Alykhan ViraA, Culley F, BobatS, LoganE, KirsteinF, WessJ, CunninghamAF, BrombacherF, SelkirkME#, HorsnellWG#. The M3 muscarinic receptor is required for optimal adaptive immunity to helminth and bacterial infection. PLoS Pathogens. 2015. Jan 28; 11(1): e1004636.(IF: 8.136)

5. Bobat S, Darby M, Mrdjen D, CookC, Logan E, Auret J, JonesE, SchnoellerC, Flores-LangaricaA, RossEA, ViraA, López-MacíasC, HendersonIR, AlexanderJ, BrombacherF, HorsnellWG#, CunninghamAF#. Natural and Vaccine-Mediated Immunity to Salmonella Typhimurium is Impaired by the Helminth Nippostrongylus brasiliensis. PLoS Neglected Tropical Diseases. 2014 Dec 4;8(12):e3341. (IF: 4.716)

6. Ndlovu H, Darby M, Froelich M, Horsnell WG, Lühder F, HünigT and Brombacher F. Inducible deletion of CD28 prior to secondary Nippostrongylus brasiliensis infection impairs worm expulsion and recall of protective memory CD4+ T cell responses. PLoS Pathogens. 2014. 6;10(2):e1003906. (IF: 8.136)

7. Thawer SG*, Horsnell WG*#, Darby M, Hoving JC, Benjamin Dewals, Cutler AJ and Brombacher F#. Lung-resident CD4+ T cells are sufficient for IL-4R dependent recall immunity to Nippostrongylus brasiliensis infection.Mucosal Immunology. 2014 Mar;7(2):239-48. (IF: 7)

8. HorsnellWG*, DarbyM*, Hoving JC, NieuwenhuizenN, McSorley HJ, Ndlovu H, BobatS, KimbergM, KirsteinF,  CutlerAJ, DeWalsB, CunninghamAF, BrombacherF#. IL-4Rassociatedantigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection. PLoS Pathogens. 2013. 9(10):e1003662. (IF: 8.136)

9. NieuwenhuizenNN, MeterJ, Horsnell  WGC, HovingJC, FickL, Sharp MF, Darby M, Parihar S, BrombacherF and LopataAL. "A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis" PLoS Neglected Tropical Diseases. 2013. 7(8):e2395. (IF: 4.716)

10. Schmidt S, Hoving JC, Horsnell WG, Mearns H, Cutler AJ, Brombacher TM, Brombacher F. Nippostrongylus-Induced Intestinal Hypercontractility Requires IL-4 Receptor Alpha-Responsiveness by T Cells in Mice.PLoS One. 2012;7(12):e52211. (IF: 3.73)

11. du Plessis N, Kleynhans L, Thiart L, van Helden PD, Brombacher F, Horsnell WG#, Walzl G#.Acute helminth infection enhances early macrophage mediated control of mycobacterial infection.Mucosal Immunology 2013 Sep;6(5):931-41. (IF 7)

12. Graham LM, Gupta V, Schafer G, Reid DM, Kimberg M, Dennehy KM, Horsnell WG, Guler R, Campanero-Rhodes MA, Palma AS, Feizi T, Kim SK, Sobieszczuk P, Willment JA, Brown GD#. The C-type lectin receptor clecsf8 (CLEC4D) is expressed by myeloid cells and triggers cellular activation through SYK kinase. Journal of Biological Chemistry. 2012 Jul 27;287(31):25964-74. (IF 4.651)

13. Nieuwenhuizen N*,  Kirstein F*,  Jayakumar J, Emedi B, Hurdayal R, Horsnell WG, Lopata AL, Brombacher F. Impairment of alternative activation of macrophages does not protect against allergic airway disease. Journal of Allergy and Clinical Immunology. 2012. 130(3):743-750.e8 (IF 12.047)

14. HorsnellWG*, Vira A*, KirsteinF, Mearns H, HovingJC, Cutler AJ, DewalsB, MyburghE, KimbergM, ArendseB, WhiteN, LopataAL, BurgerPE,  BrombacherF.  IL-4R responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections. Mucosal Immunology. 2011. Jan;4(1):83-92. (IF: 7)

15. Martins Q, Horsnell WG, Titus W, Rautenbach T, Harris S. Diet determination of the Cape mountain leopard using GPS location clusters and scat analysis.Journal of Zoology.2011. Feb; 283 (2): 81-87.

16. Dewals B, Hoving JC,  Horsnell WG,  Brombacher F. Control of Schistosoma mansoni egg-induced inflammation by CD4+CD25−CD103+FoxP3− cells is IL-10 dependent. European Journal of Immunology. 2010. Oct;40(10):2837-47. (IF: 4.94)

17. Kirstein F, Horsnell WG, Nieuwenhuizen N, Ryffel B, Lopata AL, Brombacher F. Anisakis-induced airway hyperresponsiveness is mediated by IFN-gamma in the absence of IL-4R-responsiveness. Infection & Immunity. 2010. Sep;78(9):4077-86. (IF: 4.01)

18. Kirstein F, Horsnell WG, Kuperman DA, Huang X, Erle DJ, Lopata AL, Brombacher F. Expression of IL-4R on smooth muscle cells is not necessary for development of experimental allergic asthma. Journal of Allergy and Clinical Immunology. 2010. Aug;126(2):347-354. (IF: 12.047)

19. Marillier R*, Brombacher T*, Dewals B, Leeto M, Barkhuizen M, Govender D, Kellaway L, Horsnell WG, Brombacher F. IL-4Rα-responsive smooth muscle cells increase intestinal hypercontractility and contribute to resistance during acute Schistosomiasis. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2010. Apr: 1.(IF:3.3)

20. Dewals B*, Hoving JC*, Leeto M, Marillier RG, Cutler AJ, Horsnell WG, Brombacher F. IL-4Rα responsiveness of non-CD4 T cells contributes to resistance in Schistosoma mansoni infection investigated in pan-T cell-specific IL-4Rα-deficient mice. American Journal of Pathology. 2009. Aug;175(2):706-16. (IF: 4.522)

21. Mearns H*, Horsnell WG*, Hoving JC, Dewals B, Cutler AJ, Kirstein F, Myburgh E, Arendse B, Brombacher F. IL-4 promoted T-helper 2 responses enhance Nippostrongylus brasiliensis induced pulmonary pathology. Infection & Immunity. Spotlight: Editorial  Selected Article of Significant Interest. 2008. Dec;76(12):5535-42. (IF:4.01)

22. Marillier RG, Michels C, Smith EM, Fick LC, Leeto M, Dewals B, Horsnell WG, Brombacher F. IL-4/IL-13 independent goblet cell hyperplasia in experimental helminth infections. BMC Immunology. 2008 Mar 28;9:11. (IF: 3.0)

23. Myburgh E, Horsnell WG, Cutler AJ, Arendse B, Kubo M, Brombacher F. Murine IL-4 is able to signal via chimeric human IL-4R/mouse gamma-chain receptor. Molecular Immunology. 2008 Mar; 45(5):1327-36. (IF: 2.91)

24. Parsons S*, Smith SG*, Martins Q, Horsnell WG, Gous TA, Streicher EM, Warren RM, van Helden PD, Gey van Pittius NC. Pulmonary infection due to the dassie bacillus (Mycobacterium tuberculosis complex sp.) in a free-living dassie (rock hyrax-Procavia capensis) from South Africa. Tuberculosis (Edinb). 2008 Jan; 88(1):80-83. (IF: 2.53)

25. Schwegmann A*, Guler R*, Cutler AJ, Arendse B, Horsnell WG, Flemming A, Kottmann AH, Ryan G, Hide W, Leitges M, Seoighe C, Brombacher F. Protein kinase C delta is essential for optimal macrophage-mediated phagosomal containment of Listeria monocytogenes. Proceedings of the National Academy of Sciences U S A. 2007 Oct 9; 104(41):16251-6. (IF: 9.77)

26. Horsnell WG, Cutler AJ, Hoving JC, Mearns H, Myburgh E, Arendse B, Finkelman FD, Owens GK, Erle D, Brombacher F. Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4R-deficient mice. PLoS Pathogens. 2007 Jan; 3(1):e1. (IF: 8.136)

27. Horsnell WG, Steel GJ, Morgan A. Analysis of NSF mutants reveals residues involved in SNAP binding and ATPase stimulation. Biochemistry. 2002 Apr 23; 41(16):5230-5. (IF: 3.22)

Books Edited and Book Chapters:

  1.  Roberts CW and Horsnell WG. Chapter: Effects of sex and maternal immunity on protozoan and helminth infections. In: Sex and Gender Differences in Infection and Treatments for Infectious Diseases. 2015. Eds Klein SL and Roberts CW. Springer Press 2015
  2. Horsnell WG (Editor). How helminths influence immunity to infection (Springer Press. 2014. In Production).
  3. Horsnell WG, Brombacher F. Chapter: Alternatively activated macrophages in experimental parasitic infections. In: Advances in the Immunobiology of Parasitic Diseases. 2007. Eds: LI. Terrazas and S.G.Pandalai. Research Signpost

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