Essential role for cholesterol in entry of mycobacteria into macrophages.
Mycobacteria are intracellular pathogens that can invade and survive within host macrophages, thereby creating a major health problem worldwide. The molecular mechanisms involved in mycobacterial entry are still poorly characterized. Here we report that cholesterol is essential for uptake of mycobacteria by macrophages. Cholesterol accumulated at the site of mycobacterial entry, and depleting plasma membrane cholesterol specifically inhibited mycobacterial uptake. Cholesterol also mediated the phagosomal association of TACO, a coat protein that prevents degradation of mycobacteria in lysosomes. Thus, by entering host cells at cholesterol-rich domains of the plasma membrane, mycobacteria may ensure their subsequent intracellular survival in TACO-coated phagosomes.
Gatfield
J
J
Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland.
Pieters
J
J
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D002465:Cell Movement; D002784:Cholesterol / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000502:physiology; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D008560:Membrane Fluidity; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins; D009163:Mycobacterium bovis / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*
D016177:Macrophage-1 Antigen; D008840:Microfilament Proteins; D011506:Proteins; C072061:coronin proteins; D002784:Cholesterol