Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence
Open accessAbstract
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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Virulent M. tuberculosis avoids macrophage apoptosis by inhibiting annexin I cross-linking and membrane repair, which ultimately leads to necrosis.
“In contrast, virulent M. tuberculosis avoids MO apoptosis by inhibiting annexin I cross-linking and membrane repair, which ultimately leads to necrosis (123).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [123]
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References 61 · Cited by 192
- Authors
- Gan, H., Lee, J., Ren, F., Chen, M., Kornfeld, H., & Remold, H. G.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Remold, Heinz G
- Venue
- Nature Immunology
- Published
- 2008-09-14
- Volume
- 9
- Issue
- 10
- Pages
- 1189-1197
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC5351782
- OpenAlex
- W2056045766
- Cited by
- 192
- References
- 61
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 10 · 2019: 5 · 2018: 7 · 2017: 10 · 2016: 14 · 2015: 15 · 2014: 14 · 2013: 22 · 2012: 10
- FWCI
- 11.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL064884, HL064884)
- National Institute of Allergy and Infectious Diseases (R21AI050216, AI50216, R01AI050216)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- Mycobacterium tuberculosis, annexin A1, macrophage necrosis, transglutaminase cross-linking, phosphatidylserine exposure, bacterial virulence, H37Ra, Mycobacterium tuberculosis H37Rv, attenuated mycobacteria, bacterial dissemination, antigen presentation, host-pathogen interaction
- MeSH terms
- Animals, Humans, Macrophages, Membrane Proteins, Mice, Inbred BALB C, Mycobacterium tuberculosis, Necrosis, RNA, Messenger, Tuberculosis, Virulence, Immunoblotting, Apoptosis, Annexins, Plasminogen Activator Inhibitor 2, Reverse Transcriptase Polymerase Chain Reaction, Mice
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