Skin-restricted commensal colonization accelerates skin graft rejection
| Autor: | Betty Theriault, Luqiu Chen, Maria-Luisa Alegre, Ying Wang, Anita S. Chong, Isabella Pirozzolo, Yuk Man Lei, Yasmine Belkaid, Martin Sepulveda |
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| Rok vydání: | 2019 |
| Předmět: |
Graft Rejection
Male 0301 basic medicine T-Lymphocytes Antigen-Presenting Cells Priming (immunology) Adaptive Immunity Biology Mice 03 medical and health sciences 0302 clinical medicine Staphylococcus epidermidis Animals Colonization Cell Proliferation Skin Mice Knockout Microbiota Organ Transplantation Skin Transplantation General Medicine Commensalism biology.organism_classification Acquired immune system Mice Inbred C57BL Transplantation Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Immunology Female Solid organ Lymph Research Article |
| Zdroj: | JCI Insight. 4 |
| ISSN: | 2379-3708 |
| Popis: | Solid organ transplantation can treat end-stage organ failure, but the half-life of transplanted organs colonized with commensals is much shorter than that of sterile organs. Whether organ colonization plays a role in this shorter half-life is not known. We have previously shown that an intact whole-body microbiota can accelerate the kinetics of solid organ allograft rejection in untreated colonized mice, when compared with germ-free (GF) or with antibiotic-pretreated colonized mice, by enhancing the capacity of antigen-presenting cells (APCs) to activate graft-reactive T cells. However, the contribution of intestinal versus skin microbiota to these effects was unknown. Here, we demonstrate that colonizing the skin of GF mice with a single commensal, Staphylococcus epidermidis, while preventing intestinal colonization with oral vancomycin, was sufficient to accelerate skin graft rejection. Notably, unlike the mechanism by which whole-body microbiota accelerates skin graft rejection, cutaneous S. epidermidis did not enhance the priming of alloreactive T cells in the skin-draining lymph nodes. Rather, cutaneous S. epidermidis augmented the ability of skin APCs to drive the differentiation of alloreactive T cells. This study reveals that the extraintestinal donor microbiota can affect transplant outcome and may contribute to the shorter half-life of colonized organs. |
| Databáze: | OpenAIRE |
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