Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells.

Tytuł:: Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells.
Autorzy:: Agarwal Y; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, USA.
Beatty C; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, USA.
Ho S; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, USA.
Thurlow L; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, USA.
Das A; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, USA.
Kelly S; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, USA.
Castronova I; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, USA.
Salunke R; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, USA.
Biradar S; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, USA.
Yeshi T; Hera Biolabs, Inc, Lexington, USA.
Richardson A; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, USA.
Bility M; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, USA. .
Źródło:: Scientific reports [Sci Rep] 2020 Sep 03; Vol. 10 (1), pp. 14598. Date of Electronic Publication: 2020 Sep 03.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural
Język:: English
Imprint Name(s):: Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:: Skin Transplantation*
Blood Cells/*immunology
Lymphoid Tissue/*immunology
Methicillin-Resistant Staphylococcus aureus/*immunology
Skin/*immunology
Staphylococcal Infections/*immunology
Virus Replication/*immunology
Animals ; Disease Models, Animal ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Rats ; Skin/pathology ; Staphylococcal Infections/therapy ; Transplantation, Autologous
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Grant Information:: P30 CA047904 United States CA NCI NIH HHS; R21 AI135412 United States AI NIAID NIH HHS
Entry Date(s):: Date Created: 20200905 Date Completed: 20210325 Latest Revision: 20210916
Update Code:: 20240104
PubMed Central ID:: PMC7471691
DOI:: 10.1038/s41598-020-71548-z
PMID:: 32884084
: Czasopismo naukowe

Pełny tekst

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 IL2Rγ null (NSG) mouse and Sprague-Dawley-Rag2 tm2hera Il2rγ 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.

Erratum in: Sci Rep. 2021 Sep 14;11(1):18604. (PMID: 34521965)

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