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Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence

Authors
  • Gan, Huixian1
  • Lee, Jinhee2
  • Ren, Fucheng2
  • Chen, Minjian1
  • Kornfeld, Hardy2
  • Remold, Heinz G1
  • 1 Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA , Boston (United States)
  • 2 University of Massachusetts Medical School, Worcester, Massachusetts, 01655, USA , Worcester (United States)
Type
Published Article
Journal
Nature Immunology
Publisher
Springer Nature
Publication Date
Sep 14, 2008
Volume
9
Issue
10
Pages
1189–1197
Identifiers
DOI: 10.1038/ni.1654
Source
Springer Nature
License
Yellow

Abstract

Macrophages infected with attenuated Mycobacterium tuberculosis strain H37Ra become apoptotic, which limits bacterial replication and facilitates antigen presentation. Here we demonstrate that cells infected with H37Ra became apoptotic after the formation of an apoptotic envelope on their surface was complete. This process required exposure of phosphatidylserine on the cell surface, followed by deposition of the phospholipid-binding protein annexin-1 and then transglutaminase-mediated crosslinking of annexin-1 through its amino-terminal domain. In macrophages infected with the virulent strain H37Rv, in contrast, the amino-terminal domain of annexin-1 was removed by proteolysis, thus preventing completion of the apoptotic envelope, which resulted in macrophage death by necrosis. Virulent M. tuberculosis therefore avoids the host defense system by blocking formation of the apoptotic envelope, which leads to macrophage necrosis and dissemination of infection in the lung.

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