Microbiota in heart and lung transplantation: implications for innate-adaptive immune interface

Abstract

Purpose of review Transplantation continues to be the only treatment option for end-stage organ failure when other interventions have failed. Although short-term outcomes have improved due to advances in perioperative care, long-term outcomes continue to be adversely affected by chronic rejection. Little is known about the role microbiota play in modulating alloimmune responses and potentially contributing to graft failure. Initial data have identified a correlation between specific changes of the recipient and/or donor microbiota and transplant outcomes. In this review, we will focus on recent findings concerning the complex interplay between microbiota and the innate immune system after heart and lung transplantation. Recent findings Gut microbiome derangements in heart failure promote an inflammatory state and have lasting effects on the innate immune system, with an observed association between increased levels of microbiota-dependent metabolites and acute rejection after cardiac transplantation. The lung allograft microbiome interacts with components of the innate immune system, such as toll-like receptor signalling pathways, NKG2C+ natural killer cells and the NLRP3 inflammasome, to alter posttransplant outcomes, which may result in the development of chronic rejection. Summary The innate immune system is influenced by alterations in the microbiome before and after heart and lung transplantation, thereby offering potential therapeutic targets for prolonging allograft survival.

Microbiosis in lung allotransplantation and xenotransplantation: State of the art and future perspective

“…The microbiota could exert its immune modular effect beyond colonization by the pathway of type I interferons and nuclear factor‐ΚB pathway activation as well as induce IL‐10 + B cells and suppress T‐cell activation [ 52 , 53 , 54 ]. Lower airway microbiota could intrinsically accommodate the local milieu and have been subjected to altered interaction with the local innate immune system [ 55 ]. Infection with S. aureus and Listeria monocytogenes resulted in broken tolerance, and further microbes could alter the intensity or kinetics of acute rejection [ 56 ].…”

“…The leading cause of death in adult lung transplant recipients beyond 1 year is chronic lung allograft dysfunction (CLAD) [ 55 ], which has been recognized as the reason for poor long‐term outcomes. Respiratory infections are a widely recognized risk factor for CLAD development.…”