Article abstract
Nature Immunology 10, 899 - 906 (2009)
Published online: 28 June 2009 | doi:10.1038/ni.1758
Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair
Maziar Divangahi1,3, Minjian Chen1,3, Huixian Gan1, Danielle Desjardins1, Tyler T Hickman1, David M Lee1, Sarah Fortune2, Samuel M Behar1,3 & Heinz G Remold1,3
Abstract
Induction of macrophage necrosis is a strategy used by virulent Mycobacterium tuberculosis (Mtb) to avoid innate host defense. In contrast, attenuated Mtb causes apoptosis, which limits bacterial replication and promotes T cell cross-priming by antigen-presenting cells. Here we show that Mtb infection causes plasma membrane microdisruptions. Resealing of these lesions, a process crucial for preventing necrosis and promoting apoptosis, required translocation of lysosomal and Golgi apparatus–derived vesicles to the plasma membrane. Plasma membrane repair depended on prostaglandin E2 (PGE2), which regulates synaptotagmin 7 (Syt-7), the calcium sensor involved in the lysosome-mediated repair mechanism. By inducing production of lipoxin A4 (LXA4), which blocks PGE2 biosynthesis, virulent Mtb prevented membrane repair and induced necrosis. Thus, virulent Mtb impairs macrophage plasma membrane repair to evade host defenses.
- Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
- These authors contributed equally to this work.
Correspondence to: Heinz G Remold1,3 e-mail: hremold@rics.bwh.harvard.edu
Correspondence to: Samuel M Behar1,3 e-mail: sbehar@rics.bwh.harvard.edu
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