INVertebrate IMmune memORY: specificity and mechanisms of immune memory in the Lophotrochozoan snail Biomphalaria glabrata – INVIMORY

a global transcriptomic approach and a targeted proteomic analysis of plasmatic factor were used in combination with RNA interference to describe and characterize the molecular determinants involved in B. glabrata immune priming. Genetic and epigentic processes that regulate the expression patterns of the identified molecular candidates were investigated.This work provides the first demonstration of the molecular processes supporting immune priming in an invertebrate model.

following a primo infection by the metazoan parasite Schistosoma mansoni, snails are fully protected against a secondary challenge. Moreover, this protection decreases with increasing neutral genetic distance between the parasites. Microscopic analyses revealed that the specific resistance of B. glabrata to secondary exposure to S. mansoni relies on humoral factors. A whole snail RNA sequencing approach allowed us to identify molecular candidates. Pathogen recognition receptors such as FREPs, C-type lectins, Beta-1,3-glucan binding protein and Hemagglutinin/amebocyte aggregation factors and immune effector such as the cytotoxic/cytolytic compounds proteases, reactive oxygen species and Biomphalysin appeared to be involved in S. mansoni neutralization and killing.
This results and our expertise led us to participate in a new ANR on molecular basis of trans-generational immune priming in the beetle tenebrio molitor starting in january 2015.

We hypothezised that the better protection observed following secondary infection involves specific repertoires of B. glabrata immune receptors mobilized to target certain subsets of S. mansoni genotypes. Understanding how these molecules mediate and regulate the specificity of this immune priming defence deserved now further investigations.
Finally, the present project could have important socioeconomic and public health impacts. Indeed Biomphalaria snails are important invertebrates due to their role in the transmission of schistosomiasis. Schistosomiasis or bilharzia is a tropical parasitic disease affecting 200 million humans in 74 countries, causing 200,000 deaths annually. Consequently, significant attention has been paid to freshwater snails because of their medical and epidemiological importance as intermediate hosts for Schistosoma parasites. A better understanding of the immunobiological interactions and of the compatibility (susceptibility/resistance status) between the invertebrate host Biomphalaria glabrata and its parasite Schistosoma mansoni could be of valuable importance in the discovery of new ways to prevent and/or control schistosomiasis diseases by limiting the parasite in the field.

The scientific production during these first 18 months is 3 papers in international peer reviewed journals (Plos Neglected Tropical disease, Fish Shellfish Immunology, Developmental and Comparative Immunology). Seven national and international presentations in congres. Two posters and 1 oral communication at IMMUNINV2014 in Dijon, France ; 1 oral presentation at SIP2014 in Mainz, Germany and 3 posters at REID2015 in Lyon, France.

The question of whether immune memory is the privilege of vertebrate animals is controversial and remains under intense questioning. The current prevailing paradigm is that solely vertebrates possess the mechanisms of immune memory through their adaptive immune response which displays the ability (i) to recognize antigens with a high level of specificity provided by a vast immune receptor repertoire created by somatic hypermutation and recombinatorial diversification and, (ii) to mount a stronger secondary response using again the same receptors amplified through the multiplication of memory T and B cells. Until recently and because none of these diversified molecules and memory cells were discovered in invertebrates, the prevailing view was that these animals have no acquired adaptive immunity, and that their immune system was restricted to innate and “non-specific” mechanisms.
Recently, several interesting studies have shaken this paradigm and provided evidences that the immune defence of invertebrates is far more complex and specific than previously thought. Moreover some studies evidenced that the invertebrate antiparasitic response may be “primed” in a sustainable manner, leading to the failure of secondary parasitic infections. These immune responses were described as acquired resistance or sustained response and were named “immune priming” for invertebrates. As molecular and cellular mechanisms of immune priming have not been described so far, the distinction between priming or immune memory remains ambiguous and the existence of immune memory in invertebrates remains controversial.
Recently, we have shown that immune priming or memory in the Lophotrochozoan snail Biomphalaria glabrata was highly specific against its metazoan parasite, the trematode Schistosoma mansoni. Thus in the present project we investigate the molecular basis of this specific immune memory in B. glabrata. The general scope of the project is (i) to analyze the molecular and cellular processes involved in immune priming and in specificity of immune priming, (ii) to analyze the level of diversification or polymorphism of these immune molecules to explain the specificity and finally, (iii) understand the diversity and evolution of the immune memory response in invertebrates.