also show that this antimicrobial immune response can be triggered by immune cells’ memory of previous encounters with bacteria, further complicating the body’s ability to accept a new organ. are saving lives.
“Previously, we thought the reason why human transplanted organs were less acceptable in sheltered laboratory animals was that humans can have cross-reactive immune memory reactions in the body. organ cells and memory responses are more difficult to suppress with drugs, says Maria-Luisa Alegre, MD, PhD, Professor of Medicine at UChi Chicago and senior author of the study. Now, we’ve found that not only do the memory cells recognize the organ itself as the problem, but also the memory responses recognize the bacteria in that organ.”
Two separate immune responses
The success of organ transplants depends on the type of organ. Lungs and small intestine are notoriously difficult to transplant and have a shorter survival time. Statistics show that within 5 years of surgery, 41% of lung transplant recipients and 54% of bowel transplant recipients reject their transplant, compared with organs such as the kidney (only 27% reject) and heart (23%). One theory is that the lungs and intestines, but not the kidneys and heart, are exposed to bacteria from the air and the digestive system, and that organ recipients are enhancing the immune response to more than just organs. but also with the bacteria in those organs.
In a previous study, Alegre and her team showed that when mice were transplanted with colonized skin, Staphylococcus epidermidis (S. epi)a common bacterium found on human skin, S. epi causes low-grade inflammation in the graft. The team then wondered whether the host elicited a distinct immune response against the bacteria in the graft beyond an “allergic response,” or a better understood response to foreign cells in the tissue, and whether both can damage the puzzle piece.
“The commensal bacteria in the graft are different from the recipient’s general bacteria because each individual contains a unique set of bacteria, so the host can also consider these bacteria foreign,” Alegre said. . “We think it’s possible that these two distinct immune responses (host versus graft and host against bacteria) could work synergistically or synergistically to induce a stronger immune response against graft and explain why the half-life of bacterial organs is shorter.”
Coping with a lifelong immune memory
In the new study, the researchers used mice from the gnotobiotic facility in UChi Chicago that were carefully raised in a sterile environment and free from bacterial colonization. The team transplanted skin from donor mice that are genetically identical to recipients to avoid allergies. The mice received an immune T-cell response against the graft when it was first invaded with S. epi, but not when it is left sterile. This immune response damaged the skin graft, but not by much.
Alegre and her team then tested to see if previous immune exposure to the same bacteria caused greater damage to the graft inhabited by the same bacteria, so they spread the virus. infected some mice S. epi before inoculating them, let them develop memory responses to the bacteria. When these mice were then given skin grafts with the same bacteria, the immune response was much stronger and significantly damaged the new tissue. This is important because transplant patients are exposed to many bacteria and other microorganisms through cuts, scrapes, infections and daily diet.
Most importantly, when they transplanted genetically different skin graft mice and performed microbiome simulations like most human organ transplants, they found that the drugs inhibited immunostaining prolongs transplant survival in dormant central mice in mice with anti-bacterial memory.
“That explains why when you have a lung or bowel transplant, the patient does worse and has to receive higher levels of immunosuppression than when you transplant sterile organs,” Alegre said. “You don’t just have to deal with an anti-graft response, but also an anti-bacterial response to the graft.”
The study, “Host-versus-host immune responses involved in colonized solid organ transplant rejection,” was supported by the National Institutes of Health. Other authors include Isabella Pirozzolo, Martin Sepulveda, Luqiu Chen, Ying Wang, Yuk Man Lei, Zhipeng Li, Rena Li, Husain Sattar, Betty Theriault, and Anita Chong from the University of Chicago; and Yasmine Belkaid from the NIH.