Regulation of hydrogen peroxide release in circulating hemocytes of the planorbid snail Biomphalaria glabrata

Abstract

Biomphalaria spp. serve as obligate intermediate hosts for the human blood fluke Schistosoma mansoni. Following S. mansoni penetration of Biomphalaria glabrata, hemocytes of resistant snails migrate towards the parasite, encasing the larva in a multicellular capsule resulting in its destruction via a cytotoxic reaction. Recent studies have revealed the importance of hydrogen peroxide and nitric oxide (H 2 O 2 , NO) in parasite killing [1,2]. It is assumed H 2 O 2 and NO production is tightly regulated although the specific molecules involved remain largely unknown. Consequently, the potential role of cell signaling pathways in B. glabrata hemocyte H 2 O 2 production was investigated by evaluating the effects of specific inhibitors of selected signaling proteins. Results suggest that both ERK and p38 MAPKs are involved in the regulation of B. glabrata H 2 O 2 release in response to stimulation by PMA and galactose-conjugated BSA. However, the involvement of the signaling proteins PKC, PI 3 kinase and PLA 2 differs between PMA-and BSA-gal-induced H 2 O 2 production.

Larval excretory-secretory products from the parasite Schistosoma mansoni modulate HSP70 protein expression in defence cells of its snail host, Biomphalaria glabrata

“…As the parasite transforms from a miracidium into a mother sporocyst, it releases ciliary epidermal plates and a variety of molecules from its surface and excretes a range of molecules from its excretory pore, these being jointly referred to as excretory-secretory products (ESPs; Lodes and Yoshino 1989); the protein fraction, comprising larval transformation proteins has recently been analysed by proteomics (Wu et al 2009). ESPs from platyhelminths generally consist of antioxidant enzymes, protease inhibitors, cysteine proteases, small HSPs, glycolytic enzymes, mucins, calcium, ion-binding proteins and other unknown proteins (Connors et al 1991;Guillou et al 2007;Humphries and Yoshino 2008;Lodes and Yoshino 1989;Roger et al 2008;Wu et al 2009;Zelck and Von Janowsky 2004). These parasite-derived molecules can influence the behaviour of B. glabrata defence cells (haemocytes) by affecting their motility, adhesion, ability to phagocytose or encapsulate large antigens and produce reactive oxygen species and intracellular nitric oxide (NO; Connors et al 1991;Connors and Yoshino 1990;Humbert and Coustau 2001;Loker et al 1992;Lodes and Yoshino 1990;Zahoor et al 2009).…”

“…These strains are therefore invaluable for studying snail-schistosome interactions in the context of parasite survival. Larval stage ESPs are thought to assist the survival of developing sporocysts in a susceptible snail host by interacting with haemocytes via cell surface receptors and modulating the activities of cell signalling pathways, such as the extracellular signal-regulated kinase (ERK) pathway that regulates cellular responses including cell spreading, NO and hydrogen peroxide production (Bayne 2009;Humphries and Yoshino 2008;Johnston and Yoshino 1996;Johnston and Yoshino 2001;Walker 2006;Zahoor et al 2008;Zahoor et al 2009). In the present study, we report for the first time that intracellular HSP70 protein levels in haemocytes from schistosome-susceptible and schistosomeresistant snails are reduced following exposure to S. mansoni larval ESPs.…”

Identification of differentially expressed genes in Oncomelania hupensis chronically infected with Schistosoma japonicum

“…Although the current understanding of schistosome and snail biology during the infection process is still incomplete, especially regarding the snail immunity (Bayne, 2009), a variety of molecules have been identified and may be associated with schistosome survival or snail defense mechanisms, including certain proteolytic enzymes such as cysteine proteases (Lodes and Yoshino, 1989;Guillou et al, 2007a;Humphries and Yoshino, 2008;Ittiprasert et al, 2010), receptor recognition molecules (e.g., fibrinogen-related proteins (FREPs) and lectin (Johnston and Yoshino, 2001;Hertel et al, 2005;Zhang et al, 2007;Ittiprasert et al, 2010)), molecules related to cell adhesion and signaling pathways (Goodall et al, 2006;Lockyer et al, 2007b;Zhang et al, 2007;Ittiprasert et al, 2010), and immune regulation-like epitope mimics (Plows et al, 2005;Lockyer et al, 2007b;Lehr et al, 2008). Most of the above studies aimed to decipher the differences in gene regulation between schistosome-resistant and schistosome-susceptible snails, focusing on the acute stage of schistosome-snail infection (within minutes to hours of the infection) but not chronic infection (up to >2 months) (Bayne, 2009).…”

Identification of nuclear factor kappaB (NF-κB) binding motifs in Biomphalaria glabrata

“…Similarly, previous studies suggest p38 MAPK plays a role in immune responses in B. glabrata. To illustrate, p38 MAPK was demonstrated to play a role in hemocyte in vitro H 2 O 2 production (Goodall et al, 2004;Humphries and Yoshino, 2008). This is of particular significance, as the production of H 2 O 2 is considered an anti-schistosome defense mechanism, employed by some strains of B. glabrata (Hahn et al, 2001).…”