Organ transplantation is a life-saving measure that is often a last resort to treat end-stage organ failure. Organ transplantation is notoriously complicated and sometimes results in the transplant organ being rejected by the recipient’s immune system.
Organ rejection is a complex process with multiple contributing factors. For one, lymphocytes can begin to recognize antigens on the transplanted organ in the months following an organ transplantation and respond by attacking the organ. Immunosuppressant drugs are typically prescribed post-organ transplantation to prevent the body’s lymphocytes from recognizing foreign antigens and attacking the organ. Despite this intervention, an organ rejection still occurs after a substantial number of organ transplants.
New research published in the Journal of Clinical Investigation highlights a previously overlooked factor in organ transplantation: bacterial colonies living in donated organs which add to the response against the organ. This complex response decreases the efficacy of immunosuppressive drugs and increases the probability of an organ rejection.
Lungs and small intestines are two of the most difficult organs to successfully transplant. 41% of lungs and 54% of small intestines are rejected within five years of an organ transplantation. Researchers now hypothesize that this could be due to these organs’ exposure to a diverse array of microbes from the air and the digestive system, respectively.
In their experiment, the University of Chicago researchers raised mice in a sterile environment where they could not be colonized by any bacteria. The mice raised in a sterile environment then received a skin transplant. Since the donor mice were genetically identical, a response to foreign antigens could be ruled out entirely. Immune responses to the skin graft were minimal in this group of mice. In a second group of mice, infected with the bacteria S. epi before the transplantation, the immune response was much stronger and resulted in the donated organ being significantly damaged.
“That explains why when you transplant a lung or intestine, patients do less well and have to receive higher levels of immunosuppression than when you transplant sterile organs,” said Maria-Luisa Alegre, MD, PhD, senior author of the study. “You have to deal not only with the response against the graft, but also the response against the bacteria that come with the graft.”