Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA.
Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21087-92. doi: 10.1073/pnas.1011242107. Epub 2010 Nov 17.
Invertebrates lack adaptive immune systems homologous to those of vertebrates, yet it is becoming increasingly clear that they can produce diversified antigen recognition molecules. We have previously noted that the snail Biomphalaria glabrata produces a secreted lectin, fibrinogen-related protein 3 (FREP3), unusual among invertebrate defense molecules because it is somatically diversified by gene conversion and point mutation. Here we implicate FREP3 in playing a central role in resistance to a major group of snail pathogens, digenetic trematodes. FREP3 is up-regulated in three models of resistance of B. glabrata to infection with Schistosoma mansoni or Echinostoma paraensei, and functions as an opsonin favoring phagocytosis by hemocytes. Knock-down of FREP3 in resistant snails using siRNA-mediated interference resulted in increased susceptibility to E. paraensei, providing a direct link between a gastropod immune molecule and resistance to trematodes. FREP3 up-regulation is also associated with heightened responsiveness following priming with attenuated digenetic trematodes (acquired resistance) in this model invertebrate immune system.
无脊椎动物缺乏与脊椎动物同源的适应性免疫系统，但越来越明显的是，它们可以产生多样化的抗原识别分子。我们之前曾指出，光滑滨螺（Biomphalaria glabrata）会产生一种分泌型凝集素，即纤维蛋白原相关蛋白 3（FREP3），它在无脊椎动物防御分子中是不同寻常的，因为它通过基因转换和点突变而发生体细胞多样化。在这里，我们将 FREP3 牵连到在抵抗一类主要的螺类病原体——双腔吸虫中发挥核心作用。在光滑滨螺抵抗曼氏血吸虫或 Paraensei 后睾吸虫感染的三种模型中，FREP3 的表达上调，并且作为一种调理素，有利于血细胞的吞噬作用。使用 siRNA 介导的干扰对具有抗性的蜗牛进行 FREP3 敲低，导致对 Paraensei 后睾吸虫的易感性增加，这在这个模式无脊椎动物免疫系统中提供了一个腹足类免疫分子与抵抗吸虫之间的直接联系。在该模型无脊椎动物免疫系统中，FREP3 的上调也与在经过减毒双腔吸虫（获得性抗性）引发后的高度反应性有关。
