Caveolin-1 affects early mycobacterial infection and apoptosis in macrophages and mice

Yuqing Wu; Andrea Riehle; Barbara Pollmeier; Stephanie Kadow; Fabian Schumacher; Marek Drab; Burkhard Kleuser; Erich Gulbins; Heike Grassmé

doi:10.1016/j.tube.2024.102493

Caveolin-1 affects early mycobacterial infection and apoptosis in macrophages and mice

Tuberculosis (Edinb). 2024 Feb 12:147:102493. doi: 10.1016/j.tube.2024.102493. Online ahead of print.

Authors

Yuqing Wu¹, Andrea Riehle¹, Barbara Pollmeier¹, Stephanie Kadow¹, Fabian Schumacher², Marek Drab³, Burkhard Kleuser², Erich Gulbins¹, Heike Grassmé⁴

Affiliations

¹ Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
² Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
³ Unit of Nanostructural Biointeractions, Department of Immunology of Infectious Diseases, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla Street, 53-114, Wroclaw, Poland.
⁴ Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany. Electronic address: heike.gulbins@uk-essen.de.

PMID: 38547568
DOI: 10.1016/j.tube.2024.102493

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, remains one of the deadliest infections in humans. Because Mycobacterium bovis Bacillus Calmette-Guérin (BCG) share genetic similarities with Mycobacterium tuberculosis, it is often used as a model to elucidate the molecular mechanisms of more severe tuberculosis infection. Caveolin-1 has been implied in many physiological processes and diseases, but it's role in mycobacterial infections has barely been studied. We isolated macrophages from Wildtype or Caveolin-1 deficient mice and analyzed hallmarks of infection, such as internalization, induction of autophagy and apoptosis. For in vivo assays we intravenously injected mice with BCG and investigated tissues for bacterial load with colony-forming unit assays, bioactive lipids with mass spectrometry and changes of protein expressions by Western blotting. Our results revealed that Caveolin-1 was important for early killing of BCG infection in vivo and in vitro, controlled acid sphingomyelinase (Asm)-dependent ceramide formation, apoptosis and inflammatory cytokines upon infection with BCG. In accordance, Caveolin-1 deficient mice and macrophages showed higher bacterial burdens in the livers. The findings indicate that Caveolin-1 plays a role in infection of mice and murine macrophages with BCG, by controlling cellular apoptosis and inflammatory host response. These clues might be useful in the fight against tuberculosis.

Keywords: Apoptosis; Caveolin-1; Ceramide; Cytokines; Macrophages; Mycobacterium bovis Bacillus Calmette-Guérin (BCG); Tuberculosis (TB).