N-Glycosylation Protects Host from Mycobacterial Infection

Host immunity against tuberculosis (TB) is primarily mediated by macrophages. Macrophages phagocytose *Mycobacterium tuberculosis* and restrict their growth. Through a zebrafish forward genetic screen, we have identified the early steps of N-glycosylation are required for the macrophage to resist mycobacterial infections. N-glycosylation attaches an oligosaccharide molecule to nascent secretory or membrane proteins within the endoplasmic reticulum (ER) for protein folding and trafficking. Defects of N-glycosylation induce the unfolded protein response (UPR), which sensitizes infected macrophages to intrinsic apoptosis. This apoptosis differs from the cell death observed in infected wild-type cells and is not dependent on mycobacterial virulence factors. Therefore, N-glycosylation provides protection by mitigating the ER stress of protein synthesis triggered by cellular responses to mycobacterial infection.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2024

Author dc:creator

• Lyu, Bingnan

Advisor dc:contributor.advisor

• Ramakrishnan, Lalita

• Cell Death
• ER Stress
• Macrophage
• N-glycosylation
• Tuberculosis

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/896d9b2b-7444-4eb4-affe-1b9416992367/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.112837

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/374983