How TB-infected macrophages are cleared

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This process called efferocytosis is critical for clearing apoptotic cells and debris during development, tissue homeostasis, and several inflammatory conditions. We have found it to also be important in determining the fate of TB: Efficient efferocytosis that keeps pace with infected macrophage death in the granuloma will result in clearance of infection. Conversely, if apoptotic death outpaces efferocytosis, granulomas undergo necrosis, a key pathogenic event that promotes mycobacterial growth in the accumulating cell debris.

How mycobacterium-infected apoptotic cells are cleared and the fate of mycobacteria in the efferocytic macrophages is not understood. This project will use the zebrafish TB model and cultured mammalian macrophages to characterise how healthy macrophages respond to mycobacterium-infected apoptotic cells to engulf them and whether the underlying mechanisms are different from those of homeostatic (“housekeeping”) efferocytosis. It will seek to understand the fate of healthy macrophages after efferocytosis, and how their mycobacterial cargo is trafficked and processed within them.

The successful candidate will gain interdisciplinary expertise in cell biology, immunology, microbiology and infectious diseases, as well as in genetic and molecular biology, advanced microscopy, mammalian cell culture and the use of zebrafish as a disease model.

References

• https://pubmed.ncbi.nlm.nih.gov/36103894/
• https://pubmed.ncbi.nlm.nih.gov/31474371/
• https://pubmed.ncbi.nlm.nih.gov/31570833/

Competition Funded PhD Project (Students Worldwide)