{"id":8529,"date":"2016-11-23T17:05:00","date_gmt":"2016-11-23T16:05:00","guid":{"rendered":"https:\/\/news.embl.de\/?p=8529"},"modified":"2024-08-16T23:24:10","modified_gmt":"2024-08-16T21:24:10","slug":"1611-toxoplasmas-balancing-act-explained","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1611-toxoplasmas-balancing-act-explained\/","title":{"rendered":"Toxoplasma\u2019s balancing act explained"},"content":{"rendered":"\n<p>The parasite <em>Toxoplasma gondii<\/em> is a silent success. It infects up to 95% of people in many regions of the world, and most of them never know it, due to the parasite\u2019s artful manipulation of its host\u2019s immune response. <em>Toxoplasma<\/em> keeps the immune response low enough so that it can thrive, but high enough so that its human hosts generally live healthy lives and can incubate parasites. Scientists at EMBL and the Institute for Advanced Biosciences (IAB, an INSERM &#8211; CNRS &#8211; Universit\u00e9 Grenoble-Alpes research centre) have uncovered one of the ways it maintains this balance, in a paper published today in <em>Structure<\/em>.<\/p>\n\n\n\n<p>\u201cThe parasite rewires the host\u2019s inflammatory response,\u201d says Matthew Bowler, who led the research at EMBL. \u201cIt completely subverts the chain reaction that would normally trigger our body\u2019s defenses.\u201d<\/p>\n\n\n\n<p>When a cell in your body detects a parasite, it sets off a chain reaction. Inside that cell, a series of molecules activate each other until a protein called p38\u03b1 is activated and moves into the cell\u2019s nucleus. There, it turns on the genes that trigger the inflammatory response. Among other things, the purpose of that response is to eliminate the pathogen. One would expect parasites like <em>Toxoplasma<\/em> to want to subdue that response, but Mohamed-Ali Hakimi and colleagues at IAB discovered a few years ago that <em>Toxoplasma<\/em> secretes a protein, GRA24, which does just the opposite: it activates and controls our inflammatory response.<\/p>\n\n\n\n<blockquote class=\"vf-blockquote\"><p>The parasite rewires the host\u2019s inflammatory response<\/p><\/blockquote>\n\n\n\n<p>Bowler and Hakimi discovered that GRA24 bypasses the cell\u2019s chain reaction, activating p38\u03b1 directly, and pulling it into the nucleus to turn on inflammatory response genes. Using a combination of techniques, they found that the <em>Toxoplasma<\/em> protein attaches itself much more strongly to p38\u03b1 than the cell\u2019s own proteins do. So by producing a protein that binds directly, and very tightly, to p38\u03b1, <em>Toxoplasma<\/em> controls the level of the inflammatory response and sustains it by making it inaccessible to the proteins that would usually turn it off. This is why <em>Toxoplasma<\/em> isn\u2019t considered a serious health threat except for pregnant women and people with compromised immune systems.<\/p>\n\n\n\n<p>This research has generated a new way to assess the efficacy of anti-inflammatory drugs, many of which are designed to block p38\u03b1. So far it has been difficult to assess how effective they are, because scientists haven\u2019t had a good way to produce an active form of p38\u03b1 in the lab. In producing GRA24 bound to p38\u03b1, Bowler, Hakimi and colleagues \u2013 with the help of EMBL\u2019s Protein Expression and Purification Core Facility \u2013 created just that. The tight interaction with the parasite protein keeps p38\u03b1 in its active state, so researchers can now subject it to the drugs they\u2019d like to test, and evaluate how well they block p38\u03b1\u2019s active site, which the <em>Toxoplasma<\/em> protein doesn\u2019t interfere with.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Parasite\u2019s method of rewiring our immune response leads to novel tool for drug tests<\/p>\n","protected":false},"author":8,"featured_media":8533,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[474,37,32,3612,3684,4726,1748,35,4724],"embl_taxonomy":[],"class_list":["post-8529","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-collaboration","tag-grenoble","tag-health","tag-host-pathogen-interaction","tag-infection-biology","tag-parasite","tag-press-release","tag-structural-biology","tag-toxoplasma"],"acf":{"article_intro":"<p>Parasite\u2019s method of rewiring our immune response leads to novel tool for drug tests<\/p>\n","related_links":[{"link_description":"","link_url":""},{"link_description":"","link_url":""},{"link_description":"","link_url":""}],"article_sources":[{"source_description":"<p>Pelegrini E <em>et al.<\/em> <em>Structure<\/em>, published online 23 November 2016. DOI: 10.1016\/j.str.2016.10.011<\/p>\n","source_link_url":"http:\/\/dx.doi.org\/10.1016\/j.str.2016.10.011"}],"vf_locked":false,"featured":false,"color":"#007B53","show_featured_image":false,"in_this_article":false,"youtube_url":"","mp4_url":"","video_caption":"","translations":false,"press_contact":"EMBL Generic","field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"source_article":false,"article_translations":false,"languages":""},"embl_taxonomy_terms":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Toxoplasma\u2019s balancing act explained | EMBL Grenoble<\/title>\n<meta name=\"description\" content=\"Parasite\u2019s method of rewiring our immune response leads to novel tool for drug tests\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science\/1611-toxoplasmas-balancing-act-explained\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Toxoplasma\u2019s balancing act explained | EMBL Grenoble\" \/>\n<meta property=\"og:description\" content=\"Parasite\u2019s method of rewiring our immune response leads to novel tool for drug tests\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/1611-toxoplasmas-balancing-act-explained\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2016-11-23T16:05:00+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-08-16T21:24:10+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/11\/161123-toxoplasma_ib.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"620\" \/>\n\t<meta property=\"og:image:height\" content=\"425\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Sonia Furtado Neves\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@Aur_ora\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Sonia Furtado Neves\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1611-toxoplasmas-balancing-act-explained\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1611-toxoplasmas-balancing-act-explained\/\"},\"author\":{\"name\":\"Sonia Furtado Neves\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/d926199a955624b44dda296f396c5e68\"},\"headline\":\"Toxoplasma\u2019s balancing act explained\",\"datePublished\":\"2016-11-23T16:05:00+00:00\",\"dateModified\":\"2024-08-16T21:24:10+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1611-toxoplasmas-balancing-act-explained\/\"},\"wordCount\":485,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1611-toxoplasmas-balancing-act-explained\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/11\/161123-toxoplasma_ib.jpg\",\"keywords\":[\"collaboration\",\"grenoble\",\"health\",\"host-pathogen interaction\",\"infection biology\",\"parasite\",\"press release\",\"structural biology\",\"toxoplasma\"],\"articleSection\":[\"Science\",\"Science &amp; 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