A major limitation of current humanized mouse models is that they primarily enable the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types, including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, which contains up to 40 cell types, including nonhematopoietic cells, into immunodeficient mice (lung-only mice) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus humanized mice, lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T-cell responses following cytomegalovirus infection that control virus replication. Lung-only mice and bone marrow/liver/thymus-lung humanized mice substantially increase the number of human pathogens that can be studied in vivo, facilitating the in vivo testing of therapeutics. Implantation of lung tissue into humanized mice enables in vivo study of the human immune response to pathogens.
【저자키워드】 Microbiology, Animal disease models, 【초록키워드】 T-cell Response, Infection, lung, pathogen, cells, respiratory syncytial virus, mice, virus replication, Pathogens, in vivo, mouse model, epithelial, Analysis, Middle East, humoral, cell types, endothelial, Zika virus, lung tissue, human pathogen, human immune response, respiratory syndrome coronavirus, human lung tissue, implantation, infect, hematopoietic cells, humanized, autologous, robust, clinically, replicate, 【제목키워드】 mouse model, human pathogen,