Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

Elevated IL-6 levels are associated with increased mortality upon respiratory infection after bone marrow transplantation (#164)

Alika D Collinge 1 , Rachel D Kuns 1 , Sophie C Hamann 1 , Stuart D Olver 1 , Andrew D Clouston 2 , Kirsten M Spann 3 , Mariapia Degli-Esposti 4 , Geoffrey R Hill 5 6 , Seweryn Bialasiewicz 7 8 , Simon Phipps 3 8 9 , Antiopi Varelias 1 3 8 10
  1. Transplantation Immunology, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  2. Envoi Specialist Pathologists, Brisbane, QLD, Australia
  3. School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia
  4. Infection and Immunity Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  5. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  6. Division of Medical Oncology, University of Washington, Seattle, WA, USA
  7. School of Chemistry and Molecular Biosciences, Faculty of Science, University of Queensland, St Lucia, QLD, Australia
  8. Australian Infectious Diseases Research Centre, University of Queensland, St Lucia, QLD, Australia
  9. Respiratory Immunology, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  10. Faculty of Medicine, University of Queensland, St Lucia, QLD, Australia

Allogeneic bone marrow transplantation (alloBMT) is the curative treatment for patients with haematological malignancies providing alloimmunity to eradicate the disease and prevent relapse. However, this is associated with major complications such as graft-versus-host disease (GVHD) and opportunistic infections. Common respiratory viruses can cause severe and life-threatening infection in BMT recipients. Respiratory syncytial virus (RSV) in particular can result in pneumonitis, respiratory failure and death in up to 50% of infected patients. With no vaccines and a lack of efficacious antivirals, new treatment options are needed. Given the paucity of mechanistic data to guide clinical studies or define the basis of disease, we established a murine model of RSV infection after BMT using pneumonia virus of mice (PVM), the murine homologue of human RSV, to investigate fundamental immunological mechanisms. In contrast to syngeneic BMT, alloBMT recipients displayed high levels of mortality after PVM infection (P<0.0001), recapitulating the outcome seen in patients. Early after infection, PVM was detected at similar levels in lung tissue irrespective of transplant type (allogeneic versus syngeneic), however high viral loads persisted in alloBMT recipients, suggesting an impaired antiviral response in the presence of GVHD. Immunohistochemical analysis revealed PVM localized to alveolar epithelium and macrophages. Notably, interleukin-6 (IL-6) levels in lung tissue were significantly elevated in PVM infected alloBMT recipients compared to uninfected alloBMT (P=0.01) and syngeneic BMT (P=0.005) recipients which correlated with lung pathology. These findings implicate the Th17 differentiation pathway in mediating exacerbated immunopathology. Defining the relevance of this pathway will inform novel approaches to improve the outcome of RSV infection in alloBMT patients.