Date Published: March 25, 2016
Publisher: Public Library of Science
Author(s): Emmanuel A. Pila, Mahmoud Tarrabain, Alethe L. Kabore, Patrick C. Hanington, Matty Knight.
Schistosomiasis, a devastating disease caused by parasitic flatworms of the genus Schistosoma, affects over 260 million people worldwide especially in tropical and sub-tropical regions. Schistosomes must undergo their larval development within specific species of snail intermediate hosts, a trait that is shared among almost all digenean trematodes. This unique and long-standing host-parasite relationship presents an opportunity to study both the importance of conserved immunological features in novel immunological roles, as well as new immunological adaptations that have arisen to combat a very specific type of immunological challenge. While it is well supported that the snail immune response is important for protecting against schistosome infection, very few specific snail immune factors have been identified and even fewer have been functionally characterized. Here, we provide the first functional report of a snail Toll-like receptor, which we demonstrate as playing an important role in the cellular immune response of the snail Biomphalaria glabrata following challenge with Schistosoma mansoni. This TLR (BgTLR) was identified as part of a peptide screen of snail immune cell surface proteins that differed in abundance between B. glabrata snails that differ in their compatibility phenotype to challenge by S. mansoni. The S. mansoni-resistant strain of B. glabrata (BS-90) displayed higher levels of BgTLR compared to the susceptible (M-line) strain. Transcript expression of BgTLR was found to be very responsive in BS-90 snails when challenged with S. mansoni, increasing 27 fold relative to β-actin (non-immune control gene); whereas expression in susceptible M-line snails was not significantly increased. Knockdown of BgTLR in BS-90 snails via targeted siRNA oligonucleotides was confirmed using a specific anti-BgTLR antibody and resulted in a significant alteration of the resistant phenotype, yielding patent infections in 43% of the normally resistant snails, which shed S. mansoni cercariae 1-week before the susceptible controls. Our results represent the first functional characterization of a gastropod TLR, and demonstrate that BgTLR is an important snail immune receptor that is capable of influencing infection outcome following S. mansoni challenge.
Schistosomiasis is a devastating disease caused by parasitic flatworms of the genus Schistosoma. It affects over 260 million people worldwide especially in tropical and sub-tropical regions [1,2]. The freshwater snail Biomphalaria glabrata acts an obligate intermediate host for Schistosoma mansoni, which is the causative agent of intestinal schistosomiasis in Africa and South America. This association to human schistosomiasis has made B. glabrata one of the most extensively studied gastropods in terms of immunobiology and host-parasite interactions. This snail continues to play an important role as a model for studying the intra-molluscan aspects of the parasite lifecycle, which has gained popularity as a possible target for disease control purposes . Strains of B. glabrata have been bred that display differing compatibility phenotypes to S. mansoni infection. Strains displaying resistance such as BS-90, 13-16-R1, 10-R2 [4,5] or susceptibility such as the M-line and NMRI [6,7], serve as a means to evaluate and better understand the driving mechanisms underpinning snail resistance and susceptibility. They provide valuable tools for elucidating the specifics of these naturally occurring processes .
Biomphalaria glabrata has received tremendous research attention due to its biomedical importance as an intermediate host of the causative agent of human schistosomiasis [1,2]. In the wake of the World Health Organization’s call for global elimination of schistosomiasis by the year 2025 , there is intensified interest to understand the molecular basis of the interactions that take place between schistosomes, and their snail hosts, with a view to identifying targets or mechanisms that could be exploited in disease prevention and control efforts. As a primary determinant of compatibility between this host and parasite, the snail internal defense response constitutes one area worthy of in-depth investigation in this context.