Abstract
The human skin is a significant barrier for protection against pathogen transmission. Rodent models used to investigate human-specific pathogens that target the skin are generated by introducing human skin grafts to immunocompromised rodent strains. Infection-induced immunopathogenesis has been separately studied in humanized rodent models developed with human lymphoid tissue and hematopoietic stem cell transplants. Successful co-engraftment of human skin, autologous lymphoid tissues, and autologous immune cells in a rodent model has not yet been achieved, though it could provide a means of studying the human immune response to infection in the human skin. Here, we introduce the human Skin and Immune System (hSIS)-humanized NOD-scid IL2Rγnull (NSG) mouse and Sprague–Dawley-Rag2tm2hera Il2rγtm1hera (SRG) rat models, co-engrafted with human full-thickness fetal skin, autologous fetal lymphoid tissues, and autologous fetal liver-derived hematopoietic stem cells. hSIS-humanized rodents demonstrate the development of human full-thickness skin, along with autologous lymphoid tissues, and autologous immune cells. These models also support human skin infection following intradermal inoculation with community-associated methicillin-resistant Staphylococcus aureus. The co-engraftment of these human skin and immune system components into a single humanized rodent model could provide a platform for studying human skin infections.
Highlights
The human skin is a significant barrier for protection against pathogen transmission
The human Skin and Immune System (hSIS)‐humanized NSG mouse model supports the development of full‐thickness human skin, autologous lymphoid tissues, and human immune cells
We previously demonstrated that NSG mice support the development of human lymphoid tissues along with autologous immune cells following engraftment of fetal tissues and autologous hematopoietic stem cells[17]
Summary
The human skin is a significant barrier for protection against pathogen transmission. In vivo models for studying environmental insults and pathogens that target the skin and associated cutaneous immune cells primarily involve mice and rats[3] These rodent models have improved mechanistic understanding of human diseases; significant differences exist between the skin and immune system of humans and rodents[3, 13]. Allogeneic adult human-peripheral blood mononuclear cells (PBMCs) have been introduced into these models to mimic human immune cell-skin interactions with infectious a gents[24, 29] These mouse models demonstrate successful engraftment and development of transplanted human skin and are amenable to the transplantation of allogeneic PBMCs, said platforms are not currently coupled with the engraftment of autologous lymphoid tissues that are critical for a de novo immune response. Human fetal-derived tissues and cells provide a feasible means to develop a humanized mouse model with autologous human skin and immune system
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