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  • PA-514 Immunomodulatory activities of atorvastatin on PBMCs from successfully treated TB patients presenting with or without persisting lung inflammation – preliminary findings of StatinTB trial

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PA-514 Immunomodulatory activities of atorvastatin on PBMCs from successfully treated TB patients presenting with or without persisting lung inflammation – preliminary findings of StatinTB trial
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  1. Solima Sabeel1,2,
  2. Bongani Motaung1,2,
  3. Mumin Ozturk1,2,
  4. Karin Wolmarans3,
  5. Sandra Mukasa3,
  6. Antoneta Mashinyira3,
  7. Patrick Katoto3,
  8. Fareda Jakoet-Bassier3,
  9. Tessa Kotze4,
  10. Gunar Günther5,
  11. Friedrich Thienemann3,6,
  12. Reto Guler1,2
  1. 1University of Cape Town, Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, South Africa
  2. 2International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, South Africa
  3. 3General Medicine and Global Health (GMGH), Department of Medicine, Faculty of Health Science, University of Cape Town, South Africa
  4. 4Division of Nuclear Medicine, Groote Schuur Hospital, University of Cape Town, South Africa
  5. 5Department of Pulmonology, Inselspital, Bern University Hospital, University of Bern, Switzerland
  6. 6Department of Internal Medicine, University of Zurich, Switzerland

Abstract

Background Post-TB lung disease (PTLD) is a neglected chronic lung condition that occurs despite successful completion of TB treatment. Statins have broad-range immune-modulatory and anti-inflammatory properties with a potential to reduce PTLD and improve symptoms.

In our ongoing StatinTB trial (RIA2017T-2004; NCT04147286), we evaluate safety and efficacy of 40 mg atorvastatin to reduce persistent lung inflammation (PLI) after TB treatment in HIV-/HIV+ adults measured by 18F-FDG-PET/CT. Here we aim to investigate the ex vivo immunomodulatory activities of atorvastatin on peripheral blood mononuclear cells (PBMCs) from treated TB patients following M. tuberculosis infection.

Methods At the end of TB treatment, enrolled study participants were subjected to PET/CT scan and. PBMCs were collected at baseline and treated ex vivo with atorvastatin overnight followed by infection with M. tuberculosis (Mtb) HN878 strain. At 24 hours post infection, PBMCs were subjected to flow cytometry to evaluate inflammatory cell surface markers and cell populations. Confocal microscopy was performed to measure phagosome maturation (Rab-7), phagolysosome fusion (Cathepsin-D and LAMP-3) and autophagy (LC3B). CFU and Tunnel assays were conducted to measure intracellular Mtb growth and apoptosis.

Results Ex-vivo treatment of PBMC with atorvastatin significantly reduced the intracellular growth of Mtb as measured by CFU assay. Atorvastatin treatment significantly reduced the expression of inflammatory cell surface markers (CD11b and CD16) and decreased classical monocyte (CD14+CD16-) population measured by flow cytometry. The colocalization coefficient of Mtb with the phagosome marker (Rab-7), phagolysosome markers (Cathepsin-D and LAMP-3) and autophagy marker (LC3B) were significantly enhanced by atorvastatin as measured by confocal microscopy. Apoptosis was significantly increased by the treatment of atorvastatin.

Conclusion As a host protective mechanism atorvastatin induces phagosome and phagolysosome maturation, autophagy and apoptosis in Mtb-infected PBMCs.

https://doi.org/10.1136/bmjgh-2023-EDC.225

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