{"id":18166,"date":"2019-08-12T12:00:00","date_gmt":"2019-08-12T16:00:00","guid":{"rendered":"https:\/\/dev.inrs.ca\/scientific-breakthrough-leishmania-virulence-strategy-unveiled\/"},"modified":"2020-10-13T13:13:02","modified_gmt":"2020-10-13T17:13:02","slug":"scientific-breakthrough-leishmania-virulence-strategy-unveiled","status":"publish","type":"post","link":"https:\/\/dev.inrs.ca\/en\/news\/scientific-breakthrough-leishmania-virulence-strategy-unveiled\/","title":{"rendered":"Scientific breakthrough: Leishmania virulence strategy unveiled"},"content":{"rendered":"<div class=\"single_entry_text\">\n<style type=\"text\/css\">\ndiv,\n.single_entry_text p,\n.single_entry_text li{\n    font-size: 14px !important;\n    line-height: 18px !important;\n}<\/style>\n<div>\n<div><strong>A team from the Institut National de la Recherche Scientifique (INRS) has made a scientific breakthrough regarding the virulence strategy employed by the <em>Leishmania <\/em>parasite to infect cells of the immune system. This microorganism is responsible for Leishmaniasis, a chronic parasitic disease that affects more than 12 million people worldwide.\u00a0<\/strong><\/div>\n<div>\u00a0<\/div>\n<div>The <em>Leishmania <\/em>parasite was already known to conquer its host\u2014human or animal\u2014by sabotaging the macrophage defence system, macrophages being a type of white blood cell active in the body\u2019s frontline immune response. The mechanics of <em>Leishmania <\/em>virulence strategies, however, remained unclear.\u00a0<\/div>\n<div>\u00a0<\/div>\n<\/div>\n<div><strong><img decoding=\"async\" alt=\"\" src=\"\/sites\/default\/files\/actualites-images\/Albert-Descoteaux-et-etudiant-Guillermo-Arango-Duque-microscopie-electronique-2.jpg\" style=\"width: 640px; height: 624px;\"\/><\/strong><\/div>\n<div style=\"background:#f2f2f2;padding:10px;font-size:12px !important;\">Professor Albert Descoteaux and doctoral student Guillermo Arango Duque of INRS<\/div>\n<div>\n<div>\u00a0<\/div>\n<div>INRS professor <a href=\"http:\/\/www.dev.inrs.ca\/albert-descoteaux\">Albert Descoteaux<\/a> and his team, in collaboration with researchers from <a href=\"https:\/\/www.mcgill.ca\/\" target=\"_blank\" rel=\"noopener noreferrer\">McGill University<\/a>, <a href=\"https:\/\/www.umontreal.ca\/en\/\" target=\"_blank\" rel=\"noopener noreferrer\">Universit\u00e9 de Montr\u00e9al<\/a>, and <a href=\"http:\/\/www.tohoku.ac.jp\/en\/\" target=\"_blank\" rel=\"noopener noreferrer\">Tohoku University<\/a>, have discovered that <em>Leishmania <\/em>exploits an intracellular transport mechanism already present in macrophages to spread its virulence factors. The results of the team\u2019s research were <a href=\"https:\/\/journals.plos.org\/plospathogens\/article?id=10.1371\/journal.ppat.1007982\" target=\"_blank\" rel=\"noopener noreferrer\">published <\/a>in the journal <em>PLOS Pathogens<\/em>.<\/div>\n<div>\u00a0<\/div>\n<div>\u201cIt\u2019s like there\u2019s a train travelling among the different intracellular compartments that the parasite boards to deliver its virulence factors inside the infected cell,\u201d says Professor Descoteaux, the study\u2019s lead author. \u201cOur study sheds new light on the pathogenesis of infection.\u201d<\/div>\n<\/div>\n<div>\u00a0<\/div>\n<div>\u00a0<\/div>\n<div style=\"font-size:18px !important; color:#000; margin-bottom:5px;\"><strong>Explanations<\/strong><\/div>\n<div>\n<div><em>Leishmania <\/em>is transmitted to the mammalian host through a bite from an infected phlebotomine sand fly. The parasite has two key molecules on its surface that allow it to infect the host cell\u2019s interior: the GP63 metalloprotease and lipophosphoglycan (LPG). These are known as virulence factors.\u00a0\u00a0<\/div>\n<div>\u00a0<\/div>\n<div>Upon infecting the macrophage, <em>Leishmania <\/em>enters a parasitophorous vacuole that it hijacks with the help of virulence factors. This vacuole acts as a sort of \u201cprotective bubble\u201d against the host cell\u2019s immune defences. <em>Leishmania <\/em>creates a compartment in the host cell where it can replicate.<\/div>\n<div>\u00a0<\/div>\n<\/div>\n<div><img decoding=\"async\" alt=\"\" src=\"\/sites\/default\/files\/actualites-images\/Albert-Descoteaux-et-etudiant-Guillermo-Arango-Duque-microscopie-electronique.jpg\" style=\"width: 640px; height: 422px;\"\/><\/div>\n<div style=\"background:#f2f2f2;padding:10px;font-size:12px !important;\">Professor Albert Descoteaux and his student Guillermo Arango Duque observing who infects macrophages (electron microscopy)<\/div>\n<div>\u00a0<\/div>\n<div>\n<div>Researchers wanted to understand how the parasite\u2019s molecules reach their targets inside the infected cells and what mechanisms they employed.\u00a0<\/div>\n<div>\u00a0<\/div>\n<div>\u201cMost research teams study the impacts of virulence factors, but until now no one understood how <em>Leishmania <\/em>was able transfer virulence factors from the vacuole to the cytoplasm of the infected cell. That\u2019s what we\u2019ve just shown with our work,\u201d says the study\u2019s first author, Guillermo Arango Duque, who recently received his PhD in virology and immunology supervised by Professor Descoteaux.\u00a0<\/div>\n<div>\u00a0<\/div>\n<div>\u201cWe discovered that <em>Leishmania <\/em>co-opts the macrophage\u2019s membrane fusion machinery to export virulence factors out of the vacuole,\u201d he adds.\u00a0<\/div>\n<div>\u00a0<\/div>\n<div>\u00a0<\/div>\n<\/div>\n<div style=\"font-size:18px !important; color:#000; margin-bottom:5px;\"><strong>Interconnected cellular compartments\u00a0<\/strong><\/div>\n<div>\n<div>Since the parasite successfully transfers its virulence factors (GP63 and LPG molecules) to the other side of the vacuole\u2019s membrane, it was necessary to determine what other compartment of the infected host cell contained these factors.\u00a0<\/div>\n<div>\u00a0<\/div>\n<div>The researchers observed that most of the virulence factors were found in a compartment called the endoplasmic reticulum (ER). This compartment takes up the most space in the host cell and is connected with all other intracellular compartments. They concluded that this facilitated the spread of virulence factors within the cell.\u00a0<\/div>\n<div>\u00a0<\/div>\n<div>They then used the latest genetic technology to identify the molecules involved in intracellular trafficking that are needed to spread <em>Leishmania <\/em>virulence factors in the infected host cell. The team found that by decreasing the expression of two host cell molecules, sec22b and syntaxin-5, that are responsible for regulating intracellular traffic in the ER, they could block the spread of virulence factors in the infected cell and interfere with their actions.<\/div>\n<div>\u00a0<\/div>\n<div>\u201cTo fully understand what enables the compartment where <em>Leishmania <\/em>replicates to connect with other compartments of the infected host cell is a major step forward,\u201d Professor Descoteaux says. \u201cThis pathway could also be exploited by other intracellular microorganisms such as Mycobacterium tuberculosis, which is the agent of tuberculosis, or <em>Legionella pneumophila<\/em>, which causes Legionnaires\u2019 disease.\u201d\u00a0<\/div>\n<div>\u00a0<\/div>\n<div>The next step will be to find out to what extent, by manipulating or blocking this pathway over the long term, researchers could interfere with parasite replication without significantly altering how the cell functions.\u00a0<\/div>\n<div>\u00a0<\/div>\n<div><strong>About the article<\/strong><\/div>\n<div>\u201cThe host cell secretory pathway mediates the export of <em>Leishmania <\/em>virulence factors out of the parasitophorous vacuole\u201d by Guillermo Arango Duque, Armando Jardim, \u00c9tienne Gagnon, Mitsunori Fukuda, and Albert Descoteaux was published in PLOS Pathogens. <a href=\"http:\/\/doi.org\/10.1371\/journal.ppat.1007982\" target=\"_blank\" rel=\"noopener noreferrer\">DOI.org\/10.1371\/journal.ppat.1007982<\/a><\/div>\n<div>\u00a0<\/div>\n<div>This research was supported by funding from Canadian Institutes of Health Research (CIHR).\u00a0<\/div>\n<div>\u00a0<\/div>\n<\/div>\n<div>\u00a0<\/div>\n<div>\n<div style=\"padding:30px 39px; background:#f2f2f2;border-left:solid 6px blue;\">\n<p><strong>LEISHMANIASIS KEY FACTS<\/strong>\u00a0(source: World Health Organization)<\/p>\n<p>\u00a0<\/p>\n<ul>\n<li>There are 3 main forms of leishmaniases \u2013 visceral (also known as kala-azar and the most serious form of the disease), cutaneous (the most common), and mucocutaneous.<br \/>\n\u00a0<\/li>\n<li>The disease affects some of the poorest people on earth, and is associated with malnutrition, population displacement, poor housing, a weak immune system and lack of financial resources.<br \/>\n\u00a0<\/li>\n<li>Leishmaniasis is linked to environmental changes such as deforestation, building of dams, irrigation schemes, and urbanization.<br \/>\n\u00a0<\/li>\n<li>An estimated 700 000 to 1 million new cases and some 26 000 to 65 000 deaths occur annually.<\/li>\n<\/ul>\n<\/div>\n<div>\u00a0<\/div>\n<\/div>\n<div>\u00a0<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>A team from the Institut National de la Recherche Scientifique (INRS) has made a scientific breakthrough regarding the virulence strategy employed by the Leishmania parasite to infect cells of the immune system. This microorganism is responsible for Leishmaniasis, a chronic parasitic disease that affects more than 12 million people worldwide.\u00a0<\/p>\n","protected":false},"author":1,"featured_media":18167,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[688],"tags":[],"sectors":[679],"class_list":["post-18166","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-innover-a-linrs-en","sectors-sante-en"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v24.6 (Yoast SEO v24.6) - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Scientific breakthrough: Leishmania virulence strategy unveiled | INRS<\/title>\n<meta name=\"description\" content=\"A team from the Institut National de la Recherche Scientifique (INRS) has made a scientific breakthrough regarding the virulence strategy employed by\" \/>\n<meta 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