2. Academic Validation
  3. Macrophage-augmented intestinal organoids model virus-host interactions in enteric viral diseases and facilitate therapeutic development

Macrophage-augmented intestinal organoids model virus-host interactions in enteric viral diseases and facilitate therapeutic development

  • Nat Commun. 2025 May 14;16(1):4475. doi: 10.1038/s41467-025-59639-9.
Guige Xu # 1 2 3,  Jiangrong Zhou # 2,  Kuan Liu # 2 4,  Yining Wang 2,  Theano Tsikari 5,  Fang Qin 6,  Francijna van den Hil 5,  Patrick P C Boor 2,  Ibrahim Ayada 2,  Annemarie C de Vries 2,  Jiajing Li 2,  Shijin Jiang 1,  Dewy M Offermans 2,  Denis E Kainov 7,  Harry L A Janssen 2 8,  Maikel P Peppelenbosch 2,  Marcel J C Bijvelds 2,  Wenshi Wang 6,  Valeria V Orlova 5,  Qiuwei Pan 2,  Pengfei Li 9 10
Affiliations

Affiliations

  • 1 Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Taian, Shandong, 271018, China.
  • 2 Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
  • 3 Precision Medicine Translational Research Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • 4 Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • 5 Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands.
  • 6 Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, 221004, China.
  • 7 Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028, Trondheim, Norway.
  • 8 Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
  • 9 Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands. p.li@erasmusmc.nl.
  • 10 Precision Medicine Translational Research Center, West China Hospital, Sichuan University, Chengdu, 610041, China. p.li@erasmusmc.nl.
  • # Contributed equally.
PMID: 40368896 DOI: 10.1038/s41467-025-59639-9
Abstract

The pathogenesis of enteric viral infections is attributed to both viral replication and the resultant immune-inflammatory response. To recapitulate this complex pathophysiology, we engineer macrophage-augmented organoids (MaugOs) by integrating human macrophages into primary intestinal organoids. Echovirus 1, echovirus 6, rotavirus, seasonal coronavirus OC43 and SARS-CoV-2- known to directly invade the intestine- are used as disease modalities. We demonstrate that these viruses efficiently propagate in MaugOs and stimulate the host Antiviral response. However, rotavirus, coronavirus OC43 and SARS-CoV-2, but not the two echoviruses, trigger inflammatory responses. Acetate, a microbial metabolite abundantly present in the intestine, potently inhibits virus-induced inflammatory responses in MaugOs, while differentially affecting viral replication in macrophages and organoids. Furthermore, we provide a proof-of-concept of combining Antiviral agent with either anti-inflammatory regimen or acetate to simultaneously inhibit viral Infection and inflammatory response in MaugOs. Collectively, these findings demonstrate that MaugOs are innovative tools for studying the complex virus-host interactions and advancing therapeutic development.

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