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

Silvain Pinaud,Jean-François Allienne,Richard Galinier,Julien Portela,Marie-Aude Olive,Sylvie Kieffer-Jaquinod,Benjamin Gourbal,Fanny C Nowacki,Guillaume Mitta,Nolwenn M Dheilly,David Duval,André Théron

doi:10.1371/journal.ppat.1005361

Abstract

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.

Highlights

The environment of an invertebrate is filled with complex and changing populations of microorganisms, including potential pathogens
Given the limited options for treating S. mansoni infections, much research has focused on a better understanding of the immunobiological interactions between the invertebrate host Biomphalaria glabrata and its parasite S. mansoni
Encapsulation was never observed nor was the accumulation of hemocytes observed near the parasite (100% of the entering miracidia were killed by humoral factors) (Fig 2C)

Summary

Introduction

The environment of an invertebrate is filled with complex and changing populations of microorganisms, including potential pathogens. Recent studies have shown that the immune defenses of invertebrates are more complex and specific than previously thought, and the existence of innate immune memory or priming has been suggested [2,3,4,5,6]. The observations of invertebrate innate immune memory have been mainly phenomenological and based on ecological or phenotypic studies, and little work has addressed the potential molecular and cellular mechanisms underlying these processes. To the best of our knowledge, the existing studies investigating the molecular mechanisms of innate immune memory in invertebrates have all suggested that the cellular immune response and/or hemocyte phagocytosis is/are improved upon a subsequent encounter with the same pathogen [9,10,11]. The innate immune memory response in invertebrates has been previously described as being involved in two mechanisms, namely: i. a process of acquired resistance or sustained response that consists of a long-lasting protection against a later challenge that persists even if the pathogen is neutralized; or ii. a recalled response that consists of the ability to store information of previously met pathogens and recall it later to generate a faster and more powerful response against a subsequent exposure to the same pathogen

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Results

Discussion

Conclusion