Available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/dci Disruption of ERK signalling in Biomphalaria glabrata defence cells by Schistosoma mansoni: Implications for parasite survival in the snail host Zahida Zahoor a,b , Angela J. Davies a , Ruth S. Kirk a , David Rollinson b , Anthony J. Walker a,Ã a School of Life Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey, KT1 2EE, UK b Wolfson Wellcome Biomedical Laboratories, The Natural History Museum, Cromwell Road, London, SW7 5BD, UK Received 18 March 2008; received in revised form 20 May 2008; accepted 20 May 2008 Available online 20 June 2008 KEYWORDS Haemocyte; Haemolymph; Mollusc innate immunity; Mitogen-activated protein kinase (MAPK); Extracellular signal- regulated kinase (ERK); Immune evasion; Host–parasite interaction; Excretory–secretory products Summary Biomphalaria glabrata is an intermediate snail host for the human blood fluke Schistosoma mansoni. To survive in B. glabrata, S. mansoni must suppress the snail’s haemocyte- mediated defence response; the molecular mechanisms by which this is achieved remain largely unknown. We report here that S. mansoni excretory–secretory products (ESPs) attenuate phosphorylation of extracellular signal-regulated kinase (ERK) in haemocytes from a B. glabrata strain susceptible to S. mansoni. Whole S. mansoni sporocysts also impair ERK signalling in these cells. In striking contrast, ERK signalling in haemocytes from a B. glabrata strain refractory to schistosome infection is unaffected by ESPs or sporocysts. Effects of ESPs on ERK are similar in the presence or absence of snail plasma, thus ESPs seem to affect haemocytes directly. These findings reveal novel schistosome interference mechanisms; as ERK regulates various haemocyte defence reactions, we propose that disruption of ERK signalling in haemocytes facilitates S. mansoni survival within susceptible B. glabrata. & 2008 Elsevier Ltd. All rights reserved. Introduction Like other molluscs, the snail Biomphalaria glabrata has a potent internal defence system enabling protection against intruding pathogens. Macrophage-like immune cells called haemocytes play the major part in surveillance and removal of intruders, assisted by humoral compo- nents such as carbohydrate-recognition proteins (lectins) and proteinase inhibitors [1–3]. Haemocyte-mediated defence reactions that facilitate killing of intruding orga- nisms include phagocytosis, encapsulation, and the pro- duction of reactive oxygen and nitrogen intermediates [1,4,5]. ARTICLE IN PRESS 0145-305X/$ - see front matter & 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.dci.2008.05.014 Ã Corresponding author. Tel.: +4420 85472000; fax: +44 20 8547 7497. E-mail address: t.walker@kingston.ac.uk (A.J. Walker). Developmental and Comparative Immunology (2008) 32, 1561–1571