Common bacterial infections can cause rejection of lung transplants

A large team of surgeons and organ transplant researchers from multiple institutions across the United States have found a link between lung transplant patients infected with the bacterial P. aeruginosa and rejection of transplanted lungs.

In their research Published In the journal Science Translation Medicinethis group analyzed the history of lung transplant cases looking for patients with P. aeruginosa and lung rejection. Idaira M. Guerrero-Fonseca and Bryan G. Yipp present together with the University of Calgary Focus piece With the same journal issue that outlines the work.

The relief that patients with sick lungs experience after lung transplantation is often quickly displaced by fear of the body rejecting new lungs despite immunosuppressive drugs. Lung transplants have the lowest success rate of all organ transplants.

One team member noticed that many patients who experienced lung rejection also suffered from P. aeruginosa infection. The team wondered whether such an infectious disease played a role in transplant rejection. To investigate, they analyzed the patient's case history and found that the rate was higher than expected. This led them to conduct experiments in laboratory mice.

In the laboratory experiment, otherwise healthy laboratory mice were infected with P. aeruginosa, followed by new lungs from another mouse. The team monitored the progress and found that a test mouse infected with P. aeruginosa experienced the spread of bacteria into lymphoid tissue, and the infection killed CD4.⁺ cell. It led to the growth of the number of B cells expressing a protein called CXCR3, which is sensitive to donated lung antigens. As a result, B cells produced donor-specific antibodies, causing lung rejection.

The team also found that administering test mouse drugs that block the expression of CXCR3 by B cells inhibits the mechanisms that cause rejection, allowing mice to maintain new lungs. Thus, the team not only discovered a possible association between P. aeruginosa infection and rejection of transplanted lungs, but also found it to be a possible solution to the problem.

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