Journal
SCIENTIFIC REPORTS
Volume 10, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41598-020-71548-z
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Funding
- NIH [P30CA047904]
- National Institutes of Health (NIH)-National Institute of Allergy and Infectious Diseases (NIAID) [R21AI135412]
- National Institutes of Health (NIH)-Fogarty International Center (FIC) [D43TW010039]
- National Institute of Health
- NIH
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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 IL2R gamma (null) (NSG) mouse and Sprague-Dawley-Rag2(tm2hera) Il2r gamma (tm1hera) (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.
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