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Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria

Nature Cell Biology volume 5, pages 793–802 (2003)Cite this article

Abstract

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 σ-3 lipids behaved differently and stimulated pathogen growth. Thus, lipids can be involved in both stimulatory and inhibitory signalling networks in the phagosomal membrane.

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Figure 1: In vitro actin assembly by LBP.
Figure 2: Actin nucleation by mycobacterial phagosomes in vitro.
Figure 3: Effects of lipids on actin nucleation by live M. avium-containing phagosomes.
Figure 4: Effects of lipids on actin assembly in infected macrophages.
Figure 5: Effects of lipids on acidification and phagosome fusion with late endocytic organelles.
Figure 6: Secretion of NO and killing of mycobacteria.

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Acknowledgements

We wish to thank the following for their support and suggestions: C. Dennison, E. Elliott, H. Goodfellow, R. Goethe, A. Haas, R. Hodge, D. Holden, S. Kuznetsov, C. Roy, S. Trachtenberg, K. Unsworth, P. Valentin-Weigand and the members of the EMBL photolab, especially U. Ringeisen. E. Anes's work was supported by Fundaçâo para a Ciência e a Tecnologia (FCT) grant POCTI/38983/BCI/2001 with co-participation of the EU fund FEDER.

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  1. Elsa Anes, Mark Philipp Kühnel and Evelyne Bos: These authors contributed equally to the work.

Authors and Affiliations

  1. Molecular Pathogenesis Centre, Faculty of Pharmacy, University of Lisbon, Av. Forcas Armadas, Lisbon, 1600-085, Portugal

    Elsa Anes & Jose Moniz-Pereira

  2. EMBL, Postfach 102209, Heidelberg, 69117, Germany

    Elsa Anes, Mark Philipp Kühnel, Evelyne Bos, Anja Habermann & Gareth Griffiths

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  1. Elsa Anes
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Correspondence to Gareth Griffiths.

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Anes, E., Kühnel, M., Bos, E. et al. Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria. Nat Cell Biol 5, 793–802 (2003). https://doi.org/10.1038/ncb1036

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