Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria.
Pathogenic mycobacteria such as Mycobacterium tuberculosis and Mycobacterium avium facilitate disease by surviving intracellularly within a potentially hostile environment: the macrophage phagosome. They inhibit phagosome maturation processes, including fusion with lysosomes, acidification and, as shown here, membrane actin assembly. An in vitro assay developed for latex bead phagosomes (LBPs) provided insights into membrane signalling events that regulate phagosome actin assembly, a process linked to membrane fusion. Different lipids were found to stimulate or inhibit actin assembly by LBPs and mycobacterial phagosomes in vitro. In addition, selected lipids activated actin assembly and phagosome maturation in infected macrophages, resulting in a significant killing of M. tuberculosis and M. avium. In contrast, the polyunsaturated sigma-3 lipids behaved differently and stimulated pathogen growth. Thus, lipids can be involved in both stimulatory and inhibitory signalling networks in the phagosomal membrane.
Anes
Elsa
E
Molecular Pathogenesis Centre, Faculty of Pharmacy, University of Lisbon, Av. Forcas Armadas, 1600-085 Lisbon, Portugal.
Kühnel
Mark Philipp
MP
Bos
Evelyne
E
Moniz-Pereira
Jose
J
Habermann
Anja
A
Griffiths
Gareth
G
D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D006790:Host-Parasite Interactions / Q000187:drug effects / Q000502:physiology; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D050356:Lipid Metabolism; D008055:Lipids / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D008561:Membrane Fusion / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009159:Mycobacteriaceae / Q000378:metabolism* / Q000472:pathogenicity; D009162:Mycobacterium avium / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000199:Actins; D008055:Lipids; D009569:Nitric Oxide