Aspergillus fumigatus invasion increases with progressive airway ischemia

Area of Science:

• Transplant Immunology
• Medical Mycology
• Pathophysiology

Background:

• Aspergillus infections pose a significant threat to lung transplant recipients.
• The interaction between Aspergillus and the host immune system, particularly in the context of graft rejection, is poorly understood.
• The angiotropic nature and hypoxia tolerance of Aspergillus suggest a link to ischemia in transplanted tissues.

Purpose of the Study:

• To investigate the relationship between ischemia and Aspergillus invasion in a novel tracheal transplant model.
• To determine if progressive rejection-mediated ischemia enhances Aspergillus allograft infectivity.
• To identify ischemia as a potential risk factor for invasive Aspergillus disease post-lung transplantation.

Main Methods:

• Utilized an orthotopic tracheal transplant model in conjunction with Aspergillus infection.
• Quantified blood perfusion using Laser Doppler flowmetry and FITC-lectin.
• Measured airway tissue oxygen tension with a fiber optic microsensor.
• Assessed fungal burden and invasion depth via histopathology.

Main Results:

• Achieved 80% efficacy in creating localized tracheal Aspergillus infections, predominantly at the donor-recipient anastomosis.
• Demonstrated greater Aspergillus invasiveness in allogeneic compared to syngeneic transplants.
• Observed progressive loss of perfusion and oxygenation in allografts, correlating directly with the extent of Aspergillus invasion.
• The anastomotic site showed lower perfusion and more invasive fungal disease compared to the midtrachea.

Conclusions:

• Ischemia is identified as a significant risk factor for Aspergillus invasion in lung allografts.
• The donor-recipient anastomotic site is particularly vulnerable due to reduced perfusion and oxygenation.
• Therapeutic strategies aimed at preserving vascular health may be crucial in preventing Aspergillus infections post-transplant.