Abstract
Schistosomiasis, a neglected tropical disease, owes its continued success to freshwater snails that support production of prolific numbers of human-infective cercariae. Encounters between schistosomes and snails do not always result in the snail becoming infected, in part because snails can mount immune responses that prevent schistosome development. Fibrinogen-related protein 3 (FREP3) has been previously associated with snail defense against digenetic trematode infection. It is a member of a large family of immune molecules with a unique structure consisting of one or two immunoglobulin superfamily domains connected to a fibrinogen domain; to date fibrinogen containing proteins with this arrangement are found only in gastropod molluscs. Furthermore, specific gastropod FREPs have been shown to undergo somatic diversification. Here we demonstrate that siRNA mediated knockdown of FREP3 results in a phenotypic loss of resistance to Schistosoma mansoni infection in 15 of 70 (21.4%) snails of the resistant BS-90 strain of Biomphalaria glabrata. In contrast, none of the 64 control BS-90 snails receiving a GFP siRNA construct and then exposed to S. mansoni became infected. Furthermore, resistance to S. mansoni was overcome in 22 of 48 snails (46%) by pre-exposure to another digenetic trematode, Echinostoma paraensei. Loss of resistance in this case was shown by microarray analysis to be associated with strong down-regulation of FREP3, and other candidate immune molecules. Although many factors are certainly involved in snail defense from trematode infection, this study identifies for the first time the involvement of a specific snail gene, FREP3, in the phenotype of resistance to the medically important parasite, S. mansoni. The results have implications for revealing the underlying mechanisms involved in dictating the range of snail strains used by S. mansoni, and, more generally, for better understanding the phenomena of host specificity and host switching. It also highlights the role of a diversified invertebrate immune molecule in defense against a human pathogen. It suggests new lines of investigation for understanding how susceptibility of snails in areas endemic for S. mansoni could be manipulated and diminished.
Highlights
Schistosomiasis is one of the world’s most tenacious neglected tropical diseases, infecting an estimated 207 million people, mostly children [1]
Understanding the factors important for snail resistance to schistosome infection will facilitate new lines of investigation to 1) understand the underlying basis of compatibility between schistosomes and snails in endemic areas and how this affects transmission dynamics and control efforts; and 2) to reveal ways to manipulate natural snail populations to enhance their resistance to schistosome infections
We present the first evidence that a snail immune molecule, fibrinogen related protein 3 (FREP3), is important for successful defense against schistosome infections in Biomphalaria snails
Summary
Schistosomiasis is one of the world’s most tenacious neglected tropical diseases, infecting an estimated 207 million people, mostly children [1]. Snails are often abundant and difficult to control, and it is in snails that the cercariae infective to humans are produced in prolific numbers It takes only a single schistosome miracidium to establish a snail infection capable of producing hundreds of cercariae on a daily basis for months [2]. The amplification of schistosomes that occurs within snails creates a reoccurring problem for control efforts and is a significant obstacle for sustained prevention. It highlights the importance of understanding the dynamics of schistosome infections in snails and is the reasoning behind studies focused on characterizing the mechanistic basis for snail resistance to schistosome infection. We could potentially exploit resistance to favor development of more sustainable control strategies that go beyond today’s largely one-dimensional control programs that depend primarily on treatment of infected people with praziquantel [3]
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