The kinetics of graft rejection depend mostly on the extent of genetic disparities between organ donor and recipient, but appreciation that environmental factors may also modulate these kinetics is emerging. Indeed, we have recently shown that the microbial communities present at the time of transplantation modulate the strength of an alloresponse, with microbes present before broad-spectrum antibiotic (Abx) therapy promoting greater alloreactivity and faster rejection of minor antigen-mismatched skin grafts than those present after Abx treatment. However, whether it is intestinal or skin microbiota that is responsible for regulating the outcome of skin allografts is not known. Indeed, Abx treatment altered microbial communities in both the intestine and the skin compartments. Furthermore, fecal transfer from control or Abx-treated mice into germ-free (GF) mice by oral gavage was sufficient to recapitulate allograft rejection kinetic differences, but both intestinal and cutaneous microbiota were reconstituted in the transferred mice, presumably because mouse skin is in constant contact with feces in the cage bedding.

To determine if skin microbiota is sufficient to modulate the kinetics of skin graft rejection, we topically colonized donor and recipient GF mice with one single species of Staphylococcus epidermidis (S. epi), a common skin commensal of mice and humans, prior to skin transplantation. To prevent intestinal contamination, vancomycin, an antibiotic with high toxicity for S. epi, was added in the drinking water. This approach resulted in skin but not intestinal colonization as determined by bacterial culture of skin swabs and fecal pellets. Exclusive skin colonization by a single commensal strain of bacteria was sufficient to accelerate rejection of minor antigen-mismatched skin grafts. This effect required live bacteria as GF mice painted with heat-killed S. epi displayed rejection kinetics indistinguishable from GF controls. Topical association with live, but not heat-killed, S. epi was also sufficient to increase the number of IFNg-producing T cells in both the skin and the skin-draining lymph nodes. This study suggests that changes in the local microbiota of a colonized organ impact graft outcome, and that targeting microbial constituents in a specific anatomic compartment may be a potential therapeutic strategy for enhancing graft survival.

CITATION INFORMATION: Lei Y, Chen L, Wang Y, Chong A, Belkaid Y, Alegre M.-L. A Single Skin Commensal Strain Is Sufficient to Accelerate Skin Transplant Rejection. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress