N-Glycosylation Protects Host from Mycobacterial Infection

Abstract

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.