Survival of Mycobacteria in Macrophages Is Mediated by Coronin 1-Dependent Activation of Calcineurin
Open accessAbstract
Pathogenic mycobacteria survive within macrophages by avoiding lysosomal delivery, instead residing in mycobacterial phagosomes. Upon infection, the leukocyte-specific protein coronin 1 is actively recruited to mycobacterial phagosomes, where it blocks lysosomal delivery by an unknown mechanism. Analysis of macrophages from coronin 1-deficient mice showed that coronin 1 is dispensable for F-actin-dependent processes such as phagocytosis, motility, and membrane ruffling. However, upon mycobacterial infection, coronin 1 was required for activation of the Ca(2+)-dependent phosphatase calcineurin, thereby blocking lysosomal delivery of mycobacteria. In the absence of coronin 1, calcineurin activity did not occur, resulting in lysosomal delivery and killing of mycobacteria. Furthermore, blocking calcineurin activation with cyclosporin A or FK506 led to lysosomal delivery and intracellular mycobacterial killing. These results demonstrate a role for coronin 1 in activating Ca(2+) dependent signaling processes in macrophages and reveal a function for calcineurin in the regulation of phagosome-lysosome fusion upon mycobacterial infection.
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Calcineurin inhibitors cyclosporin or FK506 block this process, resulting in reduction of mycobacterial proliferation within macrophages.
“This process can be blocked by calcineurin-inhibitors cyclosporin or FK506, resulting in reduction of mycobacterial proliferation within macrophages (20).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [20]
Coronin activates the calcium-dependent phosphatase calcineurin, which inhibits phagosome-lysosome fusion.
“Coronin then activates the calcium-dependent phosphatase calcineurin, which inhibits phagosome-lysosome fusion (20).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [20]
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References 50 · Cited by 310
- Authors
- Jayachandran, R., Sundaramurthy, V., Combaluzier, B., Mueller, P., Korf, H., Huygen, K., Miyazaki, T., Albrecht, I., Massner, J., & Pieters, J.
- Affiliations
- University of Basel (CH)
- Institut Scientifique de Santé Publique (BE)
- The University of Tokyo (JP)
- Corresponding author
- Pieters, Jean
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 130
- Issue
- 1
- Pages
- 37-50
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2048492877
- Cited by
- 310
- References
- 50
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 11 · 2023: 11 · 2022: 20 · 2021: 22 · 2020: 16 · 2019: 15 · 2018: 20 · 2017: 12 · 2016: 17 · 2015: 22 · 2014: 20 · 2013: 15 · 2012: 20
- FWCI
- 11.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2208 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- edoc (University of Basel)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Fonds Wetenschappelijk Onderzoek (G.0376.05)
- Vlaamse regering
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- coronin 1, calcineurin, mycobacteria, macrophages, phagosome-lysosome fusion, lysosomal delivery, intracellular survival, F-actin, cyclosporine, FK506, calcium signaling, phagocytosis, ruffles
- MeSH terms
- Actins, Animals, Cells, Cultured, Chemotaxis, Cytoskeleton, Enzyme Activation, Enzyme Inhibitors, Immunosuppressive Agents, Interferon-gamma, Lysosomes, Macrophages, Male, Mice, Inbred DBA, Microfilament Proteins, Mycobacterium, Mycobacterium Infections, Phagocytosis, Phagosomes, Pinocytosis, Signal Transduction, Tacrolimus, Cyclosporine, Mice, Knockout, Calcineurin, Mice
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