Skin-restricted commensal colonization accelerates skin graft rejection

JCI Insight. 2019 Jul 16;5(15):e127569. doi: 10.1172/jci.insight.127569.


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 to germ-free (GF) or to antibiotic-pre-treated 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 (S. epi), 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. epi did not enhance the priming of alloreactive T cells in the skin-draining lymph nodes (LNs). Rather, cutaneous S. epi augmented the ability of skin APCs to drive the differentiation of alloreactive T cells. This study reveals that the extra-intestinal donor microbiota can affect transplant outcome and may contribute to the shorter half-life of colonized organs.

Keywords: Adaptive immunity; Immunology; Mouse models; T cells; Transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antigen-Presenting Cells / immunology
  • Cell Proliferation
  • Disease Models, Animal
  • Female
  • Graft Rejection / immunology*
  • Graft Rejection / microbiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota
  • Organ Transplantation
  • Skin / immunology*
  • Skin / microbiology*
  • Skin Transplantation*
  • Staphylococcus epidermidis
  • T-Lymphocytes / immunology