MI2025 – Loukas Podaropoulos

Title:
BCG priming affects inflammatory responses of the alveolar microenvironment to pulmonary aspergillosis

Abstract:
Pulmonary aspergillosis encompasses several types of infections caused by ubiquitous fungi belonging to the genus Aspergillus. Immunosuppression, derived either from past disease, including asthma, cancer, and HIV infection, or cytotoxic therapies, including organ transplantation and high-dose corticosteroid administration, create a permissive environment for conidial growth and germination. This is associated with considerable mortality regardless of antifungal treatment. Interestingly, recent clinical observations suggest that pulmonary aspergillosis is the most common infection in patients with a history of tuberculosis treatment1,2. Many such cases are misdiagnosed as relapsed tuberculosis due to similarities in clinical and radiological presentation3. Although the permanent structural lung changes succeeding treatment of tuberculosis facilitate subsequent re-infection, effects on alveolar epithelial cells and macrophages, acting as the gatekeepers to pulmonary aspergillosis, as are yet to be recognised to a similar extent.

In this project, we sought to investigate changes in the stimulation of macrophages and alveolar epithelial cells in response to challenge by Aspergillus fumigatus following priming with BCG, a vaccine strain of Mycobacterium tuberculosis. We compared responses of immortalised bone marrow derived macrophages (iBMDMs), GM-CSF differentiated bone-marrow derived macrophages (BMDMs), and A549 cells. We found that BMDM and A549 cells are more responsive to aspergillus infection compared to iBMDMs. Contrary to published data, we observed that priming with BCG leads to reductions in caspase activity for both cell types at 24h and 48h post BCG priming compared to non-primed cells. Priming also leads to increased release of proinflammatory cytokines IL-1β, IL-6, and TNFα. Lastly, we observed that BMDM and A549 priming with BCG may promote aspergillus survival.

Biography:
Loukas is a second year PhD student at the University of Manchester, currently undertaking a two-year research attachment at the Infectious Diseases Labs of A*STAR in Singapore under the supervision of Dr. Amit Singhal, Dr. Sara Gago, and Dr. Gloria Lopez-Castejon. His work focuses on the transcriptional and secretory responses of macrophages when challenged with BCG and Aspergillus fumigatus. He holds an MSc in Applied Genomics from Imperial College London and an MBiolSci in Genetics from the University of Sheffield.