{"id":3918,"date":"2020-05-08T01:28:37","date_gmt":"2020-05-08T05:28:37","guid":{"rendered":"https:\/\/mrm.research.mcgill.ca\/?p=3918"},"modified":"2020-05-08T10:09:23","modified_gmt":"2020-05-08T14:09:23","slug":"mrm-insights-comment-les-cellules-souches-se-joignent-a-la-lutte-contre-le-covid-19","status":"publish","type":"post","link":"https:\/\/mrm.research.mcgill.ca\/fr\/2020\/05\/mrm-insights-comment-les-cellules-souches-se-joignent-a-la-lutte-contre-le-covid-19\/","title":{"rendered":"MRM Insights: Comment les cellules souches intestinales se joignent \u00e0 la lutte contre le COVID-19"},"content":{"rendered":"
\"\"

Dr. Alexander Gregorieff<\/p><\/div>\n

Chaque mois, dans MRM Insights<\/strong>, un membre du R\u00e9seau MRM \u00e9crit sur les cellules souches et la m\u00e9decine r\u00e9g\u00e9n\u00e9rative d\u2019un point de vue diff\u00e9rent. Ce mois-ci, le Dr. Alexander Gregorieff<\/strong>, Professeur adjoint au D\u00e9partement de pathologie de l’IR-CUSM et membre du Comit\u00e9 ex\u00e9cutif du MRM, explique comment les cellules souches intestinales se joignent \u00e0 la lutte contre le COVID-19.<\/strong><\/p>\n

Comment les cellules souches intestinales se joignent \u00e0 la lutte contre le COVID-19.<\/h2>\n

La COVID-19 est apparue ces derniers mois comme la question la plus urgente de sant\u00e9 publique et sociale dans le monde. Bien que les estimations actuelles des taux de mortalit\u00e9 demeurent contest\u00e9es, la maladie caus\u00e9e par le SRAS-CoV-2 va de sympt\u00f4mes grippaux l\u00e9gers \u00e0 la d\u00e9tresse respiratoire aig\u00fce et \u00e0 la d\u00e9faillance de plusieurs organes. L\u2019accumulation des preuves sugg\u00e8re que les r\u00e9ponses hyper-inflammatoires conduisent \u00e0 des dommages \u00e9tendus de tissu observ\u00e9s dans les cas graves de COVID-19 1<\/sup>. Cependant, les raisons pour lesquelles certaines personnes d\u00e9veloppent des r\u00e9ponses immunitaires exacerb\u00e9es face \u00e0 ce nouveau coronavirus restent incertaines. Une \u00e9quipe de recherche dirig\u00e9e par le Dr. Irah King de l’IR-CUSM et r\u00e9cemment financ\u00e9e par l\u2019Initiative interdisciplinaire en infection et immunit\u00e9 (MI4) de McGill propose que les microbes vivant dans nos tripes puissent \u00eatre des facteurs d\u00e9terminants dans le d\u00e9veloppement de la COVID-19.<\/p>\n

Le cas des microbes intestinaux.<\/h3>\n

Bien que particuli\u00e8rement caract\u00e9ris\u00e9 par des complications respiratoires aigu\u00ebs et progressives, plusieurs rapports indiquent maintenant que la COVID-19 est \u00e9troitement associ\u00e9e aux sympt\u00f4mes gastro-intestinaux (GI), y compris la naus\u00e9e et la diarrh\u00e9e 2,3<\/sup>. Fait important, la pr\u00e9sence du SRAS-Cov-2 a \u00e9t\u00e9 constat\u00e9e dans les \u00e9chantillons de selles et les biopsies de muqueuses intestinales des personnes infect\u00e9es, m\u00eame en l\u2019absence d\u2019\u00e9chantillons pulmonaires positifs 4. Bien qu\u2019aucune \u00e9vidence des dommages intestinaux \u00e9tendus de tissu n\u2019ait \u00e9t\u00e9 rapport\u00e9e dans les patients de COVID-19, ces r\u00e9sultats t\u00f4t impliquent l\u2019intestin comme probablement un composant cl\u00e9 modulant la s\u00e9v\u00e9rit\u00e9 de la maladie.<\/p>\n

Le microbiote intestinal (une collection de bact\u00e9ries, virus, champignons et arch\u00e9es) est essentiel pour une absorption efficace des nutriments et du m\u00e9tabolisme \u00e9nerg\u00e9tique, mais donne \u00e9galement le \u00ab ton \u00bb inflammatoire des organes extra-intestinaux 5<\/sup>. En cons\u00e9quence, il a \u00e9t\u00e9 \u00e9tabli que le microbiote intestinal a des fonctions r\u00e9glementaires puissantes pendant l\u2019infection virale pulmonaire 6<\/sup>. Inversement, l\u2019am\u00e9lioration de la diversit\u00e9 du microbiote intestinal entra\u00eene une diminution de la morbidit\u00e9 et de la mortalit\u00e9 \u00e0 la suite d\u2019un d\u00e9fi mortel contre la grippe 7<\/sup>. Conform\u00e9ment \u00e0 ces \u00e9tudes, les travaux de collaboration ant\u00e9rieurs de l\u2019\u00e9quipe du Dr King et des laboratoires des Drs Maziar Divangahi et Jeff Xia de l\u2019Universit\u00e9 McGill ont montr\u00e9 que la modulation du microbiote intestinal a des effets frappants sur la r\u00e9sistance de l\u2019h\u00f4te \u00e0 l\u2019infection \u00e0 mycobacterium tuberculosis<\/em> 8<\/sup>. Sur la base de ces r\u00e9sultats, ces chercheurs se penchent maintenant sur la question de savoir s\u2019il existe un lien similaire entre le microbiote intestinal et les r\u00e9ponses immunitaires de l\u2019h\u00f4te au SRAS-CoV-2.<\/p>\n

\"\"

Photo Credit: Dr. Tanvi Anil Javkar<\/p><\/div>\n

Mod\u00e9lisation COVID-19 in a dish<\/em>.<\/h3>\n

Comme premi\u00e8re \u00e9tape pour percer ce myst\u00e8re, King et ses coll\u00e8gues souhaitent \u00e9tudier si l\u2019infection par le SRAS-CoV-2 affecte la r\u00e9ponse antimicrobienne inn\u00e9e de l\u2019\u00e9pith\u00e9lium intestinal. En effet, la paroi \u00e9pith\u00e9liale intestinale sert de barri\u00e8re redoutable contre les agents pathog\u00e8nes gr\u00e2ce \u00e0 son puissant arsenal de facteurs s\u00e9cr\u00e9t\u00e9s qui neutralisent les envahisseurs bact\u00e9riens potentiels. Dans le m\u00eame ordre d\u2019id\u00e9es, un rapport pr\u00e9c\u00e9dent a montr\u00e9 que le r\u00e9cepteur de l\u2019entr\u00e9e du SRAS-CoV-2 dans la cellule (c.-\u00e0-d. ACE-2) est exprim\u00e9 abondamment sur les cellules \u00e9pith\u00e9liales du tractus gastro-intestinal et la perte de ce r\u00e9cepteur chez la souris est li\u00e9e \u00e0 la dysbiose microbienne et aux r\u00e9ponses r\u00e9g\u00e9n\u00e9ratrices d\u00e9fectueuses dans l\u2019intestin 9<\/sup>. Afin de r\u00e9pondre \u00e0 cette question, l\u2019\u00e9quipe du Dr King, en collaboration avec le Dr. Alex Gregorieff (IR-CUSM), mettra au point un syst\u00e8me d\u2019organo\u00efdes intestinaux humains pour mod\u00e9liser l\u2019infection par le SRAS-CoV-2 dans l\u2019intestin.<\/p>\n

Les organo\u00efdes sont des syst\u00e8mes de culture cellulaire quasi physiologique maintenus par des cellules souches sp\u00e9cifiques aux tissus dans un microenvironnement 3D qui pr\u00e9sentent une fonctionnalit\u00e9 d\u2019organe similaire \u00e0 leur tissu d\u2019origine 10<\/sup>. Les organo\u00efdes ont \u00e9t\u00e9 largement utilis\u00e9s pour faire la lumi\u00e8re sur le comportement des cellules souches adultes dans la sant\u00e9 et la maladie, ainsi que pour \u00e9tudier comment les agents pathog\u00e8nes courants tels que le norovirus, l\u2019h\u00e9licobacter pylori et m\u00eame les parasites ent\u00e9riques interagissent avec l\u2019\u00e9pith\u00e9lium intestinal 11-13<\/sup>. Plus r\u00e9cemment, il y a eu une course pour exploiter les organo\u00efdes pulmonaires, endoth\u00e9liaux, r\u00e9naux et h\u00e9patiques pour \u00e9tudier l\u2019impact du SRAS-CoV-2 sur ces tissus 14-16<\/sup>. Fait important, les organo\u00efdes se sont \u00e9galement av\u00e9r\u00e9s \u00eatre des mod\u00e8les puissants pour tester de nouvelles th\u00e9rapies visant \u00e0 bloquer la capacit\u00e9 du SRAS-CoV-2 \u00e0 infecter les cellules 15<\/sup>. L\u2019\u00e9quipe de recherche de l’IR-CUSM pr\u00e9voit que ses \u00e9tudes utilisant des organo\u00efdes \u00e0 base de cellules souches r\u00e9v\u00e9leront un aper\u00e7u important de cette maladie d\u00e9vastatrice et aideront \u00e0 d\u00e9terminer si l\u2019\u00e9cosyst\u00e8me intestinal devrait \u00eatre cibl\u00e9 dans le cadre d\u2019un plan de traitement complet pour lutter contre la pand\u00e9mie de COVID-19.<\/p>\n

R\u00e9f\u00e9rences <\/i>:<\/em>
\n1. Blanco-Melo, D. et al. Imbalanced hostresponse to SARS-CoV-2 drives development of COVID-19. Cell (2020). doi:DOI: 10.1016\/j.cell.2020.04.026<\/em>
\n2. Gu, J., Han, B. & Wang, J. COVID-19: Gastrointestinal Manifestations and Potential Fecal-Oral Transmission. Gastroenterology (2020). doi:10.1053\/j.gastro.2020.02.054<\/em>
\n3. Pan, L. et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. Am. J. gastrology Pre-proof (2020).<\/em>
\n4. Xiao, F. et al. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology (2020). doi:10.1053\/j.gastro.2020.02.055<\/em>
\n5. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207\u201314 (2012).<\/em>
\n6. Ichinohe, T. et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl. Acad. Sci. U. S. A. 108, 5354\u20139 (2011).<\/em>
\n7. Rosshart, S. P. et al. Wild Mouse Gut Microbiota Promotes Host Fitness and Improves Disease Resistance. Cell 171, 1015-1028.e13 (2017).<\/em>
\n8. Khan, N. et al. Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis. Mucosal Immunol. 12, 772\u2013783 (2019).<\/em>
\n9. Hashimoto, T. et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 487, 477\u201381 (2012).<\/em>
\n10. Fatehullah, A., Tan, S. H. & Barker, N. Organoids as an in vitro model of human development and disease. Nat. Cell Biol. 18, 246\u201354 (2016).<\/em>
\n11. Wilke, G. et al. A Stem-Cell-Derived Platform Enables Complete Cryptosporidium Development In Vitro and Genetic Tractability. Cell Host Microbe 26, 123-134.e8 (2019).<\/em>
\n12. Ramani, S., Crawford, S. E., Blutt, S. E. & Estes, M. K. Human organoid cultures: transformative new tools for human virus studies. Curr. Opin. Virol. 29, 79\u201386 (2018).<\/em>
\n13. Pompaiah, M. & Bartfeld, S. Gastric Organoids: An Emerging Model System to Study Helicobacter pylori Pathogenesis. Curr. Top. Microbiol. Immunol. 400, 149\u2013168<\/em>
\n14. Zhu, N. et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 382, 727\u2013733 (2020).<\/em>
\n15. Monteil, V. et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell (2020). doi:DOI: 10.1016\/j.cell.2020.04.004<\/em>
\n16. Zhao, B. et al. Recapitulation of SARS-CoV-2 infection and cholangiocyte damage with human liver ductal organoids. Protein Cell (2020). doi:10.1007\/s13238-020-00718-6<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Chaque mois, dans MRM Insights, un membre du R\u00e9seau MRM \u00e9crit sur les cellules souches…<\/p>\n","protected":false},"author":6,"featured_media":3907,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_topic_count_hidden":0,"_bbp_reply_count_hidden":0,"_bbp_forum_subforum_count":0,"ngg_post_thumbnail":0,"footnotes":""},"categories":[162],"tags":[166,163,164,165],"class_list":["post-3918","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-mrm-insights-fr","tag-cellules-souches","tag-covid-19-fr","tag-mrm-fr","tag-stem-cells-fr"],"acf":[],"yoast_head":"\nMRM Insights: Comment les cellules souches intestinales se joignent \u00e0 la lutte contre le COVID-19 | MRM<\/title>\n<meta name=\"description\" content=\"Chaque 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