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Organoid culture systems to study host-pathogen interactions. ​

文献信息 ​

DOI10.1016/j.coi.2017.07.012
PMID28756233
期刊Current opinion in immunology
影响因子5.8
JCR 分区Q1
发表年份2017
被引次数102
关键词类器官培养, 宿主-微生物相互作用, 病原体感染, 微生物共培养, 疾病模型
文献类型Journal Article, Review
ISSN0952-7915
页码15-22
期号48()
作者Devanjali Dutta, Hans Clevers

一句话小结 ​

本研究探讨了类器官培养中宿主-微生物相互作用的最新进展，揭示了寨卡病毒、细菌及其他病毒感染与疾病（如小头畸形和癌症）之间的复杂关系。研究结果为未来在微生物-类器官共培养系统的开发和更深入理解病理机制提供了重要基础。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

类器官培养 · 宿主-微生物相互作用 · 病原体感染 · 微生物共培养 · 疾病模型

摘要 ​

近期在类器官培养中对宿主-微生物相互作用研究的进展显示出巨大的潜力，并为未来在这些系统中进行更为精细的研究奠定了基础。寨卡病毒（ZIKV）感染的类器官模型帮助我们理解其与小头畸形的关联。同样，细菌（幽门螺杆菌、艰难梭状芽孢杆菌）和病毒（诺如病毒、轮状病毒）感染的发病机制也在类器官培养中得到了精确的剖析。此外，微生物在组织中的定植与癌症等疾病之间的直接关联也得到了阐明。本文讨论了在类器官培养中宿主-微生物相互作用的最新和引人注目的研究，强调了可用于开发微生物-类器官共培养系统的各种方法。

英文摘要 ​

Recent advances in host-microbe interaction studies in organoid cultures have shown great promise and have laid the foundation for much more refined future studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral organoids have helped us understand its association with microcephaly. Similarly, the pathogenesis of bacterial (Helicobacter pylori, Clostridium difficile) and viral (Norovirus, Rotaviruses) infections have been precisely dissected in organoid cultures. Additionally, direct associations between microbial colonization of tissues and diseases like cancer have also been deciphered. Here we discuss the most recent and striking studies on host-microbe interactions in organoid cultures, highlighting various methods which can be used for developing microbe-organoid co-culture systems.

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主要研究问题 ​

  1. 在器官类培养系统中，如何优化微生物共培养条件以提高病原体感染模型的可靠性？
  2. 针对不同类型的病原体（如细菌和病毒），是否有特定的器官类模型更适合研究其致病机制？
  3. 近年来在器官类培养系统中，针对微生物与宿主相互作用的研究有哪些新的技术进展？
  4. 在研究微生物定植与癌症之间的关系时，器官类培养系统如何帮助揭示潜在的分子机制？
  5. 使用器官类培养系统研究寨卡病毒感染时，是否有发现新的生物标志物与微头畸形相关联？

核心洞察 ​

研究背景和目的 ​

近年来，宿主-微生物相互作用研究在类器官培养中的进展显著，为未来更精细的研究奠定了基础。特别是在理解某些病毒（如寨卡病毒）和细菌（如幽门螺杆菌、艰难梭状芽胞杆菌）感染的机制方面，类器官模型显示出巨大的潜力。本文旨在探讨宿主-微生物相互作用在类器官培养中的最新研究，重点介绍微生物-类器官共培养系统的开发方法。

主要方法/材料/实验设计 ​

研究主要采用类器官培养技术，模拟宿主与微生物的相互作用。以下是技术路线的概述：

Mermaid diagram
  1. 类器官培养：使用人类干细胞或其他来源的细胞构建三维类器官模型。
  2. 病毒感染模型：通过引入寨卡病毒和诺如病毒，观察其对类器官的影响。
  3. 细菌感染模型：研究幽门螺杆菌和艰难梭状芽胞杆菌对类器官的感染机制。
  4. 微生物与组织的直接关联：探讨微生物定植与疾病（如癌症）之间的关系。

关键结果和发现 ​

  • 寨卡病毒与小头症：通过类器官模型，研究人员揭示了寨卡病毒感染与小头症之间的关联。
  • 细菌感染机制：类器官培养帮助精确解析了幽门螺杆菌和艰难梭状芽胞杆菌的致病机制。
  • 微生物与癌症：研究表明，微生物在组织中的定植可能与某些癌症的发展密切相关。

主要结论/意义/创新性 ​

本研究强调了类器官作为研究宿主-微生物相互作用的强大工具，能够提供更接近生理状态的实验模型。类器官培养系统的开发为理解微生物感染的机制、评估其对宿主健康的影响提供了新的视角，并可能推动个性化医学的发展。

研究局限性和未来方向 ​

  • 局限性：当前研究主要集中在特定类型的微生物和疾病模型上，可能限制了结果的普适性。
  • 未来方向：
    • 扩展类器官模型的种类，以涵盖更多的微生物和疾病。
    • 深入研究微生物与宿主之间的复杂相互作用，尤其是在多种微生物共存的情况下。
    • 结合高通量技术，进一步揭示微生物感染的分子机制及其对宿主的长期影响。

参考文献 ​

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  9. Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function. - Jhansi L Leslie;Sha Huang;Judith S Opp;Melinda S Nagy;Masayuki Kobayashi;Vincent B Young;Jason R Spence - Infection and immunity (2015)
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引用本文的文献 ​

  1. The Use of Ex Vivo Organ Cultures in Tick-Borne Virus Research. - Jeffrey M Grabowski;Danielle K Offerdahl;Marshall E Bloom - ACS infectious diseases (2018)
  2. Human organoid cultures: transformative new tools for human virus studies. - Sasirekha Ramani;Sue E Crawford;Sarah E Blutt;Mary K Estes - Current opinion in virology (2018)
  3. Basal interferon signaling and therapeutic use of interferons in controlling rotavirus infection in human intestinal cells and organoids. - Mohamad S Hakim;Sunrui Chen;Shihao Ding;Yuebang Yin;Aqsa Ikram;Xiao-Xia Ma;Wenshi Wang;Maikel P Peppelenbosch;Qiuwei Pan - Scientific reports (2018)
  4. Human Intestinal Enteroids for the Study of Bacterial Adherence, Invasion, and Translocation. - Nina M Poole;Anubama Rajan;Anthony W Maresso - Current protocols in microbiology (2018)
  5. Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age. - Jennifer Barrila;Aurélie Crabbé;Jiseon Yang;Karla Franco;Seth D Nydam;Rebecca J Forsyth;Richard R Davis;Sandhya Gangaraju;C Mark Ott;Carolyn B Coyne;Mina J Bissell;Cheryl A Nickerson - Infection and immunity (2018)
  6. Potential application of cell reprogramming techniques for cancer research. - Shigeo Saito;Ying-Chu Lin;Yukio Nakamura;Richard Eckner;Kenly Wuputra;Kung-Kai Kuo;Chang-Shen Lin;Kazunari K Yokoyama - Cellular and molecular life sciences : CMLS (2019)
  7. Microglia innately develop within cerebral organoids. - Paul R Ormel;Renata Vieira de Sá;Emma J van Bodegraven;Henk Karst;Oliver Harschnitz;Marjolein A M Sneeboer;Lill Eva Johansen;Roland E van Dijk;Nicky Scheefhals;Amber Berdenis van Berlekom;Eduardo Ribes Martínez;Sandra Kling;Harold D MacGillavry;Leonard H van den Berg;René S Kahn;Elly M Hol;Lot D de Witte;R Jeroen Pasterkamp - Nature communications (2018)
  8. The migration and fusion events related to ROCK activity strongly influence the morphology of chicken embryo intestinal organoids. - Małgorzata Pierzchalska;Małgorzata Panek;Maja Grabacka - Protoplasma (2019)
  9. 2D- and 3D-Based Intestinal Stem Cell Cultures for Personalized Medicine. - Yuan Liu;Ye-Guang Chen - Cells (2018)
  10. A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip. - Sasan Jalili-Firoozinezhad;Francesca S Gazzaniga;Elizabeth L Calamari;Diogo M Camacho;Cicely W Fadel;Amir Bein;Ben Swenor;Bret Nestor;Michael J Cronce;Alessio Tovaglieri;Oren Levy;Katherine E Gregory;David T Breault;Joaquim M S Cabral;Dennis L Kasper;Richard Novak;Donald E Ingber - Nature biomedical engineering (2019)

... (92 更多 篇文献)

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