A large team of surgeons and organ transplant researchers affiliated with multiple institutions across the U.S. has found an association between lung transplant patients who become infected with the bacteria Pseudomonas aeruginosa and rejection of the transplanted lung.
In their study published in the journal Science Translational Medicine, the group analyzed lung transplant case histories looking for patients with P. aeruginosa and lung rejection. Idaira M. Guerrero-Fonseca and Bryan G. Yipp with the University of Calgary have published a Focus piece in the same journal issue outlining the work.
The relief that patients with sick lungs experience after a lung transplant is often quickly displaced by fear of their body rejecting the new lungs despite immunosuppressive drugs. Lung transplantation has one of the lowest rates of success of all organ transplants.
One of the team members noticed that many patients who experienced lung rejection also had a P. aeruginosa infection. The team wondered if such infections played a role in transplant rejections. To find out, they analyzed patient case histories and found the rate to be higher than expected. This prompted them to conduct experiments with lab mice.
In their lab experiments, otherwise healthy lab mice were infected with P. aeruginosa and were then given new lungs from another mouse. As the team monitored their progress, they found that the test mice infected with P. aeruginosa experienced bacterial spread to lymphoid tissue, where the infection killed CD4+ cells. That led to growth in the number of B cells expressing a protein called CXCR3, which were sensitive to antigens in the donated lungs. As a result, the B cells produced donor-specific antibodies, which led to rejection of the lungs.
The team also found that giving the test mice drugs that blocked the expression of CXCR3 by the B cells inhibited the mechanism that led to rejection, allowing the mice to keep their new lungs. Thus, the team not only found a possible association between P. aeruginosa infections and rejection of transplanted lungs, but a possible solution for the problem.
More information:
Fuyi Liao et al, Pseudomonas aeruginosa infection induces intragraft lymphocytotoxicity that triggers lung transplant antibody-mediated rejection, Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.adp1349
Idaira M. Guerrero-Fonseca et al, No tolerance for Pseudomonas in lung transplants, Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.adu6563
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Common bacterial infection may trigger lung transplant rejection (2025, February 7)
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