Background: Isolation of Pseudomonas aeruginosa (PsA) is associated with increased BAL (bronchoalveolar lavage) inflammation and lung allograft injury in lung transplant recipients (LTR). However, the effect of PsA on macrophage responses in this population is incompletely understood. We examined human alveolar macrophage (AMΦ) responses to PsA and Pseudomonas dominant microbiome in healthy LTR.
Methods: We stimulated THP-1 derived macrophages (THP-1MΦ) and human AMΦ from LTR with different bacteria and LTR BAL derived microbiome characterized as Pseudomonas-dominant. Macrophage responses were assessed by high dimensional flow cytometry, including their intracellular production of cytokines (TNF-α, IL-6, IL-8, IL-1β, IL-10, IL-1RA, and TGF-β). Pharmacological inhibitors were utilized to evaluate the role of the inflammasome in PsA-macrophage interaction.
Results: We observed upregulation of pro-inflammatory cytokines (TNF-α, IL-6, IL-8, IL-1β) following stimulation by PsA compared to other bacteria (Staphylococcus aureus (S.Aur), Prevotella melaninogenica, Streptococcus pneumoniae) in both THP-1MΦ and LTR AMΦ, predominated by IL-1β. IL-1β production from THP-1MΦ was sustained after PsA stimulation for up to 96 hours and 48 hours in LTR AMΦ. Treatment with the inflammasome inhibitor BAY11-7082 abrogated THP-1MΦ IL-1β production after PsA exposure. BAL Pseudomonas-dominant microbiota elicited an increased IL-1β, similar to PsA, an effect abrogated by the addition of antibiotics.
Conclusion: PsA and PsA-dominant lung microbiota induce sustained IL-1β production in LTR AMΦ. Pharmacological targeting of the inflammasome reduces PsA-macrophage-IL-1β responses, underscoring their use in lung transplant recipients.
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http://dx.doi.org/10.1016/j.healun.2023.04.005 | DOI Listing |
Interdiscip Cardiovasc Thorac Surg
January 2025
Critical Care Department, Finis Terrae University. Santiago, Chile.
Silicosis, a fibrotic lung disease caused by crystalline silica inhalation, presents unique challenges in lung transplantation. This case reports an unprecedented complication in a lung transplant recipient with chronic silicosis. A man in his 60 s, post left single-lung transplantation for silica-induced pneumoconiosis, developed acute respiratory deterioration following routine bronchoscopy.
View Article and Find Full Text PDFTranspl Infect Dis
January 2025
Unit of Infectious Diseases and Infection Control, ISMETT-IRCCS Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
Introduction: Infections significantly impact morbidity and mortality in lung transplant (LuTx) recipients. This survey focused on documenting current practices regarding the prevention and management of infections in LuTx in Italy.
Methods: A 52-question survey was administered online in the period from December 1, 2023, to January 31, 2024, assessing center characteristics, Tx team organization, microbiological investigations, infection prevention, and management.
Eur J Case Rep Intern Med
December 2024
Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Unlabelled: Sinusoidal obstruction syndrome (SOS) is a distinctive and potentially fatal form of hepatic injury that mainly occurs after hematopoietic-stem cell transplantation but also due to many other conditions including drug or toxin exposure. Recently, immune checkpoint inhibitors (ICIs) have revolutionised the treatment of many solid organ malignancies. Furthermore, as their use has become more widespread, rare toxicities have emerged.
View Article and Find Full Text PDFAnn Thorac Surg Short Rep
December 2024
Toronto Lung Transplant Program, Toronto General Hospital, Toronto, Canada.
Ex vivo lung perfusion (EVLP) is used to evaluate donor lungs prior to lung transplantation. Development of pulmonary edema during EVLP is generally thought to represent inflammatory breakdown of the air-fluid barrier and these lungs are declined for transplant. We present the case of a donor lung that underwent stapled wedge resection during cold storage for air leak and the subsequent development of profound (∼650 mL) pulmonary edema around the staple line during EVLP.
View Article and Find Full Text PDFAnn Thorac Surg Short Rep
December 2024
Department of Pulmonary and Critical Care Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. Although other mechanical circulatory support devices have been associated with anti-human leukocyte antigen antibody formation, including de novo donor-specific antibodies (dnDSA), it is unknown whether ECMO is a sensitizing exposure.
Methods: This was a single-center retrospective cohort study of lung transplant recipients.
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