Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection

Molecular Systems Biology

Megan L Stanifer¹  Markus Mukenhirn²  Camila Metz‐Zumaran²  Ronald Koschny³  Malte Paulsen⁴  Diana Ordoñez‐Rueda⁴  Vladimir Benes⁵  Steeve Boulant⁶  Carmon Kee⁶  Sergio Triana⁷  Clara Serger⁷  Mohammed Shahraz⁷  Theodore Alexandrov⁷ 

[1] Department of Infectious Diseases, Molecular Virology Heidelberg University Heidelberg Germany;Department of Infectious Diseases, Virology Heidelberg University Heidelberg Germany;Department of Internal Medicine IV Interdisciplinary Endoscopy Center University Hospital Heidelberg Heidelberg Germany;Flow Cytometry Core Facility European Molecular Biology Laboratory Heidelberg Germany;Genomics Core Facility European Molecular Biology Laboratory Heidelberg Germany;Research Group “Cellular Polarity and Viral Infection” German Cancer Research Center (DKFZ) Heidelberg Germany;Structural and Computational Biology Unit European Molecular Biology Laboratory Heidelberg Germany;

关键词: astrovirus;    immune response;    intestinal epithelial cells;    organoids;    single‐cell transcriptomics;   

DOI  :  10.15252/msb.20209833

来源: DOAJ

【 摘 要 】

Abstract Human intestinal epithelial cells form a primary barrier protecting us from pathogens, yet only limited knowledge is available about individual contribution of each cell type to mounting an immune response against infection. Here, we developed a framework combining single‐cell RNA‐Seq and highly multiplex RNA FISH and applied it to human intestinal organoids infected with human astrovirus, a model human enteric virus. We found that interferon controls the infection and that astrovirus infects all major cell types and lineages and induces expression of the cell proliferation marker MKI67. Intriguingly, each intestinal epithelial cell lineage exhibits a unique basal expression of interferon‐stimulated genes and, upon astrovirus infection, undergoes an antiviral transcriptional reprogramming by upregulating distinct sets of interferon‐stimulated genes. These findings suggest that in the human intestinal epithelium, each cell lineage plays a unique role in resolving virus infection. Our framework is applicable to other organoids and viruses, opening new avenues to unravel roles of individual cell types in viral pathogenesis.

【 授权许可】

Unknown