Differences in the Gene Expression Profiles of Haemocytes from Schistosome-Susceptible and -Resistant Biomphalaria glabrata Exposed to Schistosoma mansoni Excretory-Secretory Products

Abstract

During its life cycle, the helminth parasite Schistosoma mansoni uses the freshwater snail Biomphalaria glabrata as an intermediate host to reproduce asexually generating cercariae for infection of the human definitive host. Following invasion of the snail, the parasite develops from a miracidium to a mother sporocyst and releases excretory-secretory products (ESPs) that likely influence the outcome of host infection. To better understand molecular interactions between these ESPs and the host snail defence system, we determined gene expression profiles of haemocytes from S. mansoni-resistant or -susceptible strains of B. glabrata exposed in vitro to S. mansoni ESPs (20 μg/ml) for 1 h, using a 5K B. glabrata cDNA microarray. Ninety-eight genes were found differentially expressed between haemocytes from the two snail strains, 57 resistant specific and 41 susceptible specific, 60 of which had no known homologue in GenBank. Known differentially expressed resistant-snail genes included the nuclear factor kappa B subunit Relish, elongation factor 1α, 40S ribosomal protein S9, and matrilin; known susceptible-snail specific genes included cathepsins D and L, and theromacin. Comparative analysis with other gene expression studies revealed 38 of the 98 identified genes to be uniquely differentially expressed in haemocytes in the presence of ESPs, thus identifying for the first time schistosome ESPs as important molecules that influence global snail host-defence cell gene expression profiles. Such immunomodulation may benefit the schistosome, enabling its survival and successful development in the snail host.

Deep, multi-stage transcriptome of the schistosomiasis vector Biomphalaria glabrata provides platform for understanding molluscan disease-related pathways

“…Others include gastric intrinsic factor, serine/arginine-rich splicing factor 7 and NRDE-2. These genes also may be useful targets in the treatment of schistosomiasis, and our dataset can in this way act as a bridge between previous functional investigations such as [56] and sequences of presently unknown function in the nr database.…”

“…For example, [56] used a microarray-based method to identify 98 differentially expressed sequences from haemocytes of schistosome-resistant and schistosome-susceptible B. glabrata after exposure to excretory-secretory products from S. mansoni. Of these 98 EST derived sequences, 61 were at that time unable to be assigned homology to known gene families due to their short length, and therefore were excluded from further analysis in that manuscript.…”

Comparative immunogenomics of molluscs

“…Microarray studies have shown novel aspects of immunity of particular species of molluscs. For example, different strains of the gastropod B. glabrata display distinct baseline expression profiles (Lockyer et al, 2012, 2008; Zahoor et al, 2014); this snail mounts pathogen-specific immune responses to Gram (−), Gram (+) bacteria and metazoan parasites (Adema et al, 2010), and FREP3 was identified as a common feature of successful defense responses (Hanington et al, 2012, 2010). …”

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

“…At the cellular level, the snail's defense strategies include phagocytosis and cellular encapsulation of pathogens, while humoral factors include lectins, the production of oxygen radicals and a recently identified family of fibrinogen-related proteins (FREPs) (Yoshino and Coustau, 2011). These defense mechanisms likely involve changes in gene expression, and several studies show that the transcriptional profile of B. glabrata is modified in response to stressors such as gram-negative and gram-positive bacteria, mechanical wounding, and metazoan parasites Hanelt et al, 2008;Hanington et al, 2010;Ittiprasert et al, 2010;Lockyer et al, 2012;Mitta et al, 2005;Zahoor et al, 2014). Despite ample evidence of altered gene expression during immune responses in B. glabrata, the regulatory mechanisms responsible are not known.…”

“…Despite ample evidence of altered gene expression during immune responses in B. glabrata, the regulatory mechanisms responsible are not known. Transcription factors have only recently been identified in B. glabrata (Bouton et al, 2005;Kaur et al, 2015;Zhang and Coultas, 2011) and just one promoter region has ever been characterized (Yoshino et al, 1998).…”