Channel: Académie Vétérinaire de France clear
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| 1 | Académie Vétérinaire de France | Immunomodulation induced by trichinella and possible use to treat huma... | 34 | 14.2 | 25:33 | The first presentation will be made by Lilliana Sofronik, who will talk to us about the most beautiful aspects of the parasites, as a modulator, vis-à-vis of a tropor-symune. Lilliana Sofronik is a medicine immunologist. She has worked very long at Bellgrad, the Institute for Research. It is a bit equivalent to the CEA for Serbia. And Lilliana has worked under the direction of a veterinary parasyte specialist, immunology specialist and tracking specialist, who is called Costa Cooper-Lević. Good afternoon. I like to express my gratitude to Professor Jean Bocca-May and distinct academicians for inviting me to participate this meeting. And I really feel sorry that due to Southern Elnis, I am not able to participate on site. So I devoted this slide to my mentor, Professor Costa Truper-Lević, renowned immunopathicologist, who contributed a lot in the field of Trichinela and Trichinela, as well as Serbia. And he participated in implementation of artificial digestion in all water houses in Serbia during the 80s in previous century. And he also was a member of the important committee that was a joint committee between Ministry of Health and Ministry of Agriculture, with the main task to react in case of free emergency of Trichinelauses and to propose measures for better control of spreading this infection to human. I'm very proud of this slide because due to his efforts and later on efforts of my group, we were able to follow the presence of Trichinela infection in domestic peaks and in human for 60 years. But as you can see from this slide, in Serbia Parasyte, so Trichinela games, games were detected initially in peak arcases in 1918, while the first case is of human infection very counted in 1923. The improvement in swine production practices had cut prevalence of Trichinela infections in swine from 0.11 to in 1918 to less than 0.009 during the 80s. And the professor Trupero, which published a lot of papers where you can find the data for previous century. At the end of previous century, we had a big emergency of Trichinelauses during the political appeals. We had civil wars and sanctions. And we needed quite long period of time to overcome that problem. And as you can see today, we are keeping quite good control. The level of infection among domestic peaks. And we have just a small number of cases each year only during the 2021. We didn't have any case of Trichinelauses. So you can see that Trichinela provokes a lot of different kinds of problems in my country. And if you like to read the papers, that is one I published regarding the first decade of this millennium. And the second one where I also participated published by Sasha Vasilev is full of details regarding presence of Trichinela infection in the last decade of this millennium. Since you could see from the previous slide that in this millennium we had around 3000 cases of Trichinelauses with only three deaths. And the main cause of the infection was Trichinela Spiralis, although we have Trichinela Britovi in wild boars. So there were some outbreaks that have been introduced by Trichinela Britovi. But what we, as a newologist, have been very much interested in. And we are providing first help in detection of Trichinela infection presence by developing in a thinnepin and vitro diagnostic tools in direct immunofluorescence, saliser, and western blog. But besides those kind of work, we were able to see that most of patients recovered completely and had no symptoms of Trichinelauses. But some of patients in Serbia declared that they have noticed the improvement in their health condition, meaning there was absence of allergy symptoms they previously had asthma or relapses of labial health, a simple infection. All those that indicated to us that Trichinela can somehow help to healthy status of the patient and to better fight with other facts. Next slide please. I will not go to you with a lot of data that we are immunologists like to talk about. This is a complex network and communication in between parasite and different cells on the level of small intestineum. But when the parasite developed in muscle, then you can see first inflammation and that disappearance of inflammatory response. And they like to estimate that each stage of Trichinela first triggers an inflammatory response of TH1 type on the site of tissue penetration by parasite. But the parasite successfully reversed that response to TH2 type. Next slide please. Those are the nice slides prepared by it is on this premiere explaining how this amazing parasite is able to create completely new type of cell in the whole body, which name is nurse cell, you probably know that and that nurse cell is completely free of muscle specific proteins. And which had a sole purpose to serve the needs of the parasite. Next slide please. And those members of Trichinela's patients are able to form the capsule capsule is semi-perma-bilm and brain, which allows nutrients from the host and metabolic products of the of parasite to pass through. And do not allow effector cells, immunocompetent cells and are specific antibodies to hurt the parasite. So during the evolution, parasite formed this immunoprivileged place in the host body and take the host's immune respond under its wing as long as it is alive. Next slide please. We asked ourselves the same question as famous immunopiracidologist Bill and Margaret at her met a putte, can parasitic worms cure the modern world eels. So you probably know about existence of hygiene hypothesis telling that there is inverse correlation in between presence of parasitic infections and life threatening out immune diseases. And we know that the authorities like to find out how parasite can help in curing those kinds of disease. So keeping in mind that we are focused to Trichinela, we are studying what immune cells are involved, what are signaling pathways in those cells, what kind of cytokines they produce, what extra cellular vesicles, duties in communication with the host. And we are looking, is there any kind of help by a publication of nanoparticles at once that their built approach to chronic inflammatory and autoimmune diseases. Next slide please. So first we were able to show the first to show that Trichinela's spiralis infection is able to provoke amalgamation of the clinical force of VAE. It is experimental immune and so follow my light is that is used in use in animal model for human disease multiple sclerosis that is devastating autoimmune disease leading to progressive deterioration of neurological. And we have made that with my 100 muscle that that we used for infection we could successfully modulate those disease since we are over the all the science of the infection preparing control group where disease only was introduced. So duration of illness and infiltration of central nervous system very significant lead us next slide please. So we wanted to understand what are the mechanisms that are involved in this immune modulation and we were first go discovered that Trichinela's spiralis influence maturation of antigen presenting the diretic cells. To become to keep that cells in semi mature stations not the parts that don't allow those cells to become pro inflammatory mature cells but keep keep them as semi mature those kind of the diretic cells we called to therogenic cells. And they promote the shift from pro inflammatory response to anti inflammatory one that significantly delay the onset and alleviated and short into the course of the disease next slide please. Okay, this is just to be very short on the left side we you can see influence in animal model here is what we obtained in human model of the diretic cells so an animal model week you can see what is semi mature status of the cells and which molecules are expressed on the surface. The diretic cells you know have a key role in initiation of immune response during the infection but under the influence of parasite to therogenic the diretic cells became central players in the maintenance of immune tolerance and favorable candidates for self therapy of autoimmune disease. And right now there are clinical trials that are going on in Europe which apply the dose dollar of genic that the diretic cells produced under the influence of other agents not parasitic in origin in treatment of patients with multiple sclerosis what we have shown is the text literary secretary products of Trichinela induced table of human dollar of genic the diretic cells at that dose. Induction of those cells in horse engagement of multiple pattern recognition receptors that you can see on this slide we call them told like receptor to for then the diretic cells specific icon free grabbing non integrity in this design molecule and knows accept the next slide please. Until I can see next slide just to mention that this kind of cell influence that shift to take to and the regulatory cells next slide yes. This is just showing the what kind of pathways are going down stream in the cell upon interaction of parasitic antigens with the toll like receptors and we show that there is transient activation of her can man active. And then we have a lot of information about the activation of P 38 meaning that this on this way parasite will stop production of proinformatory cytokines from those cells next slide please. In addition to the use of inflammatory phenotype and function dollar of genic the diretic cells explain express some dollar of genic markers such as either one and the three and those cells enable that the regulatory cells are doing that way. So to either one dependent manner next slide please those are the results that we obtain by a fox system meaning that we use that fluorescent method in analysis and here you can see that this cell activated with the extreme secondary secretary pro took treated and the diretic cells educated the diretic cells exhibit suppressing feature. Those these cells inhibit the proliferation of peripheral blood mononuclear cells and functional properties of educated and the dredic cells are preserved even in inflammatory environment this oppressive activity could be ascribed to increase percentage of tear regulatory cells that appear after the influence of a trigonal educated the dredic cells next slide please. So when we approved that trick infection can dump or prevent EA we found protective effect effect of infection could be established by not by alive infection agent but also by different ways other ways to be successfully treated animals with educated and breathing cells. And on that way we also ameliorated the disease also the prophylactic application of extraterrestriary products for its components by itself exerted beneficial effect on outcome of EA next slide please. So here is the example how everything looks like when we apply dedicated and the dredic cells you can see that there is a lower level of maximal clinical score cumulative index that be shortened duration of the illness and we compare the truth effect or. By the dredic cells with the fact of infection we can see the almost the same result that this stimulated the dredic cells maintains reach towards to pH to meaning aisle four presence and the regulatory cytokine aisle 10 while there is the crease of the levels of interferogram and dial 17 which are prone for the cytokines next slide please. This is the picture how how we investigated the presence of regulatory Fox speaker cells and you can see the percentage of those cells is significantly increased in the screen as well as in population of spinal cord infiltrating cells of rats treated with those then the dredic cells educated next slide please. Our group was first one who found the trichinela spiral is like many other methods releases extra cell or vesicles is biological nanostructures of ESL one products for which we proved to possess immunomodulatory properties and this shed new light on the mechanisms by which trichinela spiral is delivery information to the host immune system since extracellular vesicles or exosomes here carry all types of biomole. The molecules proteins lipids and NA fragments of DNA metables beta ball it's small molecules and represent the first fundamental mode of intercellular communication along with direct cellular contact and exchange of soluble markers next slide please. You can see here the exosomes from trichinela next slide please. And those are the effects we follow they exhibited the application of access cell or vesicles exhibit the similar effects on monocyte and retic deregated cells they inducing completely matured and retic cells with all our genetic properties which remains stable in inflammatory environment next slide please. And those cells exhibited limited all of the moral authority capacity on this cell responder responders and as I mentioned the remains table upon introduction of in inflammatory stimulus. What we wanted now to do at the end we wanted to find the most favorable if I can say approach how to treat humans not to use infusion of educated the dretic cells but to find a way how we can easily apply components of trichinela and during the disease so we designed the delivery system in a form of implant. And we resisted of biodegradable polylactic public policy BLGA in non of fibers and ESL and antigens and so we performed implantation 21 days before the eA induction and you can see that we achieved very similar results in taming and unallureating the disease. So now we are showing again what is going on the systemic level in clean cells i'm here pointing out on the same cytokines like you had opportunity to see this is what is going on in the target tissue inspire in spine spinal cord so lower level of infiltrating cells presence of the regulatory and macrophages is increased next slide please. So here we have production of those anti inflammatory cytokines the 10 and I'll for again and the origin of that I'll 10 he's coming not only from CD4 plus T cells but also from regulatory T cells regulatory B cells and macrophages possibly alternatively activated next slide please. So it looks obvious that beside the beneficial effect of health administration and animal model of autoimmune disease and the biggest results from few clinical trials which use the live warm as a therapy. This kind of therapy faces a lot of obstacles and carries risk for the host organism from that reason we need to learn more from the canal is master of immunomodulation about component it uses and mechanism situatilized striving to contribute novelty, rapid approach not only to multiple sclerosis but also other autoimmune diseases. So next slide please I like to acknowledge the work of members of my group some national institutions that are involved in as well as collaboration with institutes from France from Japan from Italy from United States and United Kingdom thank you very much for your attention. Many thanks really enough for your excellent presentation with a lot of facts and immunological points are there any questions we have time for one or two questions. A question by Isabelle Valley. Hello, Liana nice to see you and of course we would prefer to have you in presence here but thanks for your presentation just while general question but within your yes and to Jen. Do you think that Tivolo is the major on Tigen that is involved in what you observe or do you think about particular protein within the yes and to Jen. Hello Isabelle I hope that soon I will feel better enough to meet you some of my parents and I'm also missing my presence among you over there in place. That is a nice and interesting question because as immunologists and knowing well that the extradite secretary products are consisted of many glycoproteins and in that glycosolide part that the type of analysis is specific and characteristic for the canal. I thought that it will be very hard task to produce a convenient antigen with not only consisting of protein part of the molecule but also to consist of Tivols and that only on that way we can imitate what parasite is doing. But I think that Tivolo has important roles since we although we were able to show that parasite interact with those glycoprote with the receptors on the surface of the cells. But I had the opportunity to read a paper from our colleagues in Japan who that I mentioned before who's succeeded to just apply recombinant protein from the canal upsell the spiral is not clearly causally the toll and to tame and to cure somehow in animal model. The model science of autoimmune disease which name is psoriasis it is a skin disease or also autoimmune disease. So the question is open because we really don't know how important Tivolos is in that Tolerogenic process induction probably time will show that I don't have a real response on your questions. Thank you again and thanks a lot. Many thanks for your presentation. | ↗ |