Lung transplant recipients are highly vulnerable to infections, with Pseudomonas aeruginosa being a leading cause of bacterial pneumonia. Researchers have found in a new study that infection with P. aeruginosa independently predicts antibody-mediated rejection (AMR) in these patients. Further early detection of such infections is suggested as a potential strategy for predicting and managing AMR, helping to develop effective prevention and treatment approaches. This study was published in the journal Science Translational Medicine by Fuyi L. and colleagues.Lung transplant patients are at very high risk of developing bacterial pneumonia, and a common cause was P. aeruginosa. To verify this, an observational study was conducted on retrospective analysis to establish a relation between Pseudomonas infection and AMR. The presence of such correlation was especially clear in cystic fibrosis, who are considered to be susceptible to chronic Pseudomonas colonization.Key FindingsInfection by Pseudomonas aeruginosa conferred an increased risk for AMR among lung transplant recipients, particularly those with cystic fibrosis.Using mouse models, researchers established that P. aeruginosa rapidly infiltrated bronchial-associated lymphoid tissues. This resulted in the death of regulatory Foxp3+CD4+ T cells through apoptosis.The bacterial T3SS exotoxin T was sufficient to induce graft-resident Foxp3+CD4+ T cell apoptosis.The depletion of regulatory T cells led to Myd88-dependent expansion of T-bet+ and CXCR3+ germinal center and memory B cells.CXCR3+ B cells were significantly elevated in lung transplant recipients diagnosed with AMR.CXCR3 blockade in mice prevented AMR despite P. aeruginosa infection.The study authors concluded that P. aeruginosa is an important AMR contributor in lung transplant patients. This research result suggests direct involvement of bacterial infections in the transplant rejection process, thereby pointing toward the possibility of using drugs that target this pathway to mitigate AMR.Reference:Liao, F., Zhou, D., Cano, M., Liu, Z., Scozzi, D., Tague, L. K., Byers, D. E., Li, W., Sivapackiam, J., Sharma, V., Krupnick, A. S., Frank, D. W., Kreisel, D., Kulkarni, H. S., Hachem, R. R., & Gelman, A. E. (2025). Pseudomonas aeruginosa infection induces intragraft lymphocytotoxicity that triggers lung transplant antibody-mediated rejection. Science Translational Medicine, 17(784). https://doi.org/10.1126/scitranslmed.adp1349