Identification and characterization of five transcription factors that are associated with evolutionarily conserved immune signaling pathways in the schistosome-transmitting snail Biomphalaria glabrata.

Innate immunity consists of humoral and cellular components that play a vital role in regulation of defense responses to various pathogens in vertebrates and invertebrates. Recent studies have shown that Rel/DIF (dorsal-related immunity factor), Relish, STAT (signal transducer and activator of transcription) and CREB (cAMP response element-binding protein) transcription factor associated pathways are evolutionarily conserved across the animal kingdom. Although the primary role and general structure of the pathways in immunity have been revealed in many invertebrates, particularly arthropods, almost nothing is known about these pathways in the freshwater snail Biomphalaria glabrata, the intermediate host of the human blood fluke Schistosoma mansoni, which is a causative agent of human schistosomiasis. Given the central role of transcription factors (TF) in controlling expression of effector genes, understanding the role of a given TF is essential to obtaining insight into the general function of the corresponding signaling pathway. To better understand the immunity of B. glabrata, we investigated five homologues of TFs that have been shown to be associated with multiple prominent immune signaling pathways based on the considerable data reported from a wide phylogenetic range of animals. In this study we identified and characterized cDNAs of five TFs from B. glabrata, designated BgRelish, BgRel, BgSTAT1, BgSTAT2 and BgCREB, for the first time. Among the five TFs, Relish is first reported in Lophotrochozoa, one of three superphyla in Metazoa. Our identification of class I (BgRelish) and II (BgRel) NF-κB in B. glabrata suggests the two pathways, Toll-like receptor (TLR) and immune deficiency (IMD)-like pathways, are present in the superphylum Lophotrochozoa. Preliminarily expression studies indicate these TF-associated pathways may be involved in the snail's anti-schistosome response. This study not only advances our understanding of the snail's defenses, but also provides new perspectives about the evolution of animal immunity.