Biomphalaria glabrata immunity: Post-genome advances

Abstract

The freshwater snail, Biomphalaria glabrata, is an important intermediate host in the life cycle for the human parasite Schistosoma mansoni, the causative agent of schistosomiasis. Current treatment and prevention strategies have not led to a significant decrease in disease transmission. However, the genome of B. glabrata was recently sequenced to provide additional resources to further our understanding of snail biology. This review presents an overview of recently published, post-genome studies related to the topic of snail immunity. Many of these reports expand on findings originated from the genome characterization. These novel studies include a complementary gene linkage map, analysis of the genome of the B. glabrata embryonic (Bge) cell line, as well as transcriptomic and proteomic studies looking at snail-parasite interactions and innate immune memory responses towards schistosomes. Also included are biochemical investigations on snail pheromones, neuropeptides, and attractants, as well as studies investigating the frontiers of molluscan epigenetics and cell signaling were also included. Findings support the current hypotheses on snail-parasite strain compatibility, and that snail host resistance to schistosome infection is dependent not only on genetics and expression, but on the ability to form multimeric molecular complexes in a timely and tissue-specific manner. The relevance of cell immunity is reinforced, while the importance of humoral factors, especially for secondary infections, is supported. Overall, these studies reflect an improved understanding on the diversity, specificity, and complexity of molluscan immune systems.

Fig. 1.. Schistosoma mansoni intramolluscan larval stages in Biomphalaria glabrata and biological tools used in host-parasite studies.

The life cycle of the trematode Schistosoma mansoni uses the planorbid snail Biomphalaria glabrata as an obligatory intermediate host. Infection of snails is initiated when eggs (a) produced by adult S. mansoni worms found in the human host are released into the environment. Upon contact with fresh water, the eggs hatch into miracidia (b). The miracidium is a free-living and motile larval stage of the parasite that after locating a snail host, it will penetrate its exposed epithelia. Inside snail tissues, miracidia transform into the primary (mother) sporocyst (c), the first intramolluscan larval stage. After 24–48 h post-infection, primary sporocysts start migrating to other snail tissues, preferentially the digestive gland. In these internal tissues, germinal cells within primary sporocysts develop into secondary (daughter) sporocysts (d), which on their own will produce more sporocysts. Alternatively, secondary sporocysts will also produce cercariae (e), the last intramolluscan larval stage, that once matured will break out of snail tissues and swim in the aquatic environment in search of a new vertebrate host. Cercariae can penetrate the skin of humans and start a new cycle of infection when adult worms (f) develop, pair and start producing eggs. Studies in snail immunity utilize a variety of biological tools including various developmental stages of snails including embryos and juveniles (g), the B. glabrata embryonic (Bge) cell line (h), cellular components such as hemocytes (i), and other snail species for example Bulinus spp. and Oncomelania spp. (j)

Fig. 2.. Protein domains in B. glabrata TEP family.

Graphical representation of the putative conserved domains identified in the B. glabrata BB02 TEP sequences. The conserved domains found in all B. glabrata TEP-sequences have similar content and organization as those reported in other invertebrate and vertebrate TEPs. The National Center for Biotechnology Information (NCBI) Conserved Domain Database (CDD) (http://www.ncbi.nlm.nih.gov/cdd) was utilized for TEP domain nomenclature and abbreviations. A2M_N = MG2 (macroglobulin) domain of alpha-2-macroglobulin; A2M_N_2 = Alpha-2macroglobulin family N-terminal region; A2M = Alpha-2-macroglobulin family, includes the C-terminal region of the alpha-2-macroglobulin family; Complement_C3_C4_C5 = Proteins similar to C3, C4 and C5 of vertebrate complement, thioester bond located within the structure of C3 and C4; A2M_2 = Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP); A2M_comp = Complement component region of the alpha-2-macroglobulin family; A2M_recep = Receptor domain region of the alpha-2-macroglobulin family; NTR_ complement_C345C = NTR/C345C domain, NTR domains found in the C-termini of complement C3, C4 and C5; NTR = UNC-6/NTR/C345C module, sequence similarity between netrin UNC-6 and C345C complement protein family members; C345C = Netrin C-terminal Domain. The characteristic GCGEQ thioester domain is labeled with “TED” and regions labeled with an asterisk do not completely align wi4th the representative GCGEQ residues, having one or more dissimilar amino acids for the thioester domain sequence. No label signifies that no thioester domain was identified. The intervals of each domain and the length of each sequence are illustrated to scale with the most up-to-date amino acid length labeled at the 3′-end.

Fig. 3.. Putative IL-17- and TNF-signaling pathways in B. glabrata.

TRAF2 = TNF receptor associated factor 2; AP1 = activator protein 1; NF-κB = nuclear factor κB; TNF = tumor necrosis factor; TNFR = TNF receptor; TACE = TNF-α-converting enzyme; IL-17 = interleukin 17; IL-17R = IL-17 receptor; red arrow indicates outside-in signaling via a TNF receptor; blue arrows indicate outside-in signaling via IL-17 and TNF receptors. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)