A Comparative Study of Human Pluripotent Stem Cell-Derived Macrophages in Modeling Viral Infections.
Yaxuan ZhangHui QiuFuyu DuanHaoran AnHuimin QiaoXingwu ZhangJing-Ren ZhangQiang DingJie NaPublished in: Viruses (2024)
Macrophages play multiple roles in innate immunity including phagocytosing pathogens, modulating the inflammatory response, presenting antigens, and recruiting other immune cells. Tissue-resident macrophages (TRMs) adapt to the local microenvironment and can exhibit different immune responses upon encountering distinct pathogens. In this study, we generated induced macrophages (iMACs) derived from human pluripotent stem cells (hPSCs) to investigate the interactions between the macrophages and various human pathogens, including the hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Streptococcus pneumoniae . iMACs can engulf all three pathogens. A comparison of the RNA-seq data of the iMACs encountering these pathogens revealed that the pathogens activated distinct gene networks related to viral response and inflammation in iMACs. Interestingly, in the presence of both HCV and host cells, iMACs upregulated different sets of genes involved in immune cell migration and chemotaxis. Finally, we constructed an image-based high-content analysis system consisting of iMACs, recombinant GFP-HCV, and hepatic cells to evaluate the effect of a chemical inhibitor on HCV infection. In summary, we developed a human cell-based in vitro model to study the macrophage response to human viral and bacterial infections; the results of the transcriptome analysis indicated that the iMACs were a useful resource for modeling pathogen-macrophage-tissue microenvironment interactions.
Keyphrases
- hepatitis c virus
- pluripotent stem cells
- sars cov
- endothelial cells
- respiratory syndrome coronavirus
- rna seq
- single cell
- induced pluripotent stem cells
- gram negative
- human immunodeficiency virus
- inflammatory response
- immune response
- stem cells
- induced apoptosis
- antimicrobial resistance
- cell migration
- dna methylation
- wastewater treatment
- dendritic cells
- bone marrow
- machine learning
- mesenchymal stem cells
- toll like receptor
- artificial intelligence
- cell cycle arrest
- hiv infected
- stress induced
- data analysis