a somatically diversified defense factor, frep3, is a determinant of snail resistance to schistosome infection不良多元化防御因子,frep3,是蜗牛的行列式抗血吸虫感染.pdfVIP

A Somatically Diversified Defense Factor, FREP3, Is a Determinant of Snail Resistance to Schistosome Infection 1 2 2 Patrick C. Hanington *, Michelle A. Forys , Eric S. Loker 1 Environmental Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada, 2 Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, New Mexico, United States of America 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 snai