A Shift from Cellular to Humoral Responses Contributes to Innate Immune Memory in the Vector Snail Biomphalaria glabrata

Discoveries made over the past ten years have provided evidence that invertebrate antiparasitic responses may be primed in a sustainable manner, leading to the failure of a secondary encounter with the same pathogen. This phenomenon called “immune priming” or "innate immune memory" was mainly phenomenological. The demonstration of this process remains to be obtained and the underlying mechanisms remain to be discovered and exhaustively tested with rigorous functional and molecular methods, to eliminate all alternative explanations. In order to achieve this ambitious aim, the present study focuses on the Lophotrochozoan snail, Biomphalaria glabrata, in which innate immune memory was recently reported. We provide herein the first evidence that a shift from a cellular immune response (encapsulation) to a humoral immune response (biomphalysin) occurs during the development of innate memory. The molecular characterisation of this process in Biomphalaria/Schistosoma system was undertaken to reconcile mechanisms with phenomena, opening the way to a better comprehension of innate immune memory in invertebrates. This prompted us to revisit the artificial dichotomy between innate and memory immunity in invertebrate systems.

近十年来的研究成果提供了相关证据，表明无脊椎动物的抗寄生虫应答可被以可持续方式致敏，使得宿主在再次遭遇同种病原体时出现免疫失败。这一被称为“免疫致敏（immune priming）”或“固有免疫记忆（innate immune memory）”的现象，目前仍主要处于现象学研究阶段。该过程的实证验证尚未完成，其潜在机制也有待通过严谨的功能与分子实验方法进行全面探究与验证，以排除所有竞争性解释。为达成这一具有前瞻性的研究目标，本研究聚焦于近期被报道存在固有免疫记忆的冠轮动物总门螺类——光滑双脐螺（Biomphalaria glabrata）。本文首次提供证据显示，在固有免疫记忆的形成过程中，宿主的免疫应答会从细胞免疫应答（包囊化作用）转向体液免疫应答（双脐溶素（biomphalysin））。我们通过对光滑双脐螺/血吸虫（Schistosoma）体系中该过程的分子特征进行解析，将机制与现象加以关联，为更好地理解无脊椎动物的固有免疫记忆开辟了道路。这一研究也促使我们重新审视无脊椎动物系统中固有免疫与记忆性免疫之间人为构建的二元对立关系。