Mycobacterium tuberculosis Cpn60.2 (GroEL2) blocks macrophage apoptosis via interaction with mitochondrial mortalin
| Autor: | Zakaria Hmama, Alexander Yuen, Vijender Singh, Sunil Joseph |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mycobacterial persistence QH301-705.5 Host–pathogen interaction Science Antigen presentation Mitochondrion Biology General Biochemistry Genetics and Molecular Biology Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Macrophage Biology (General) Phagosome Host-pathogen interaction Intra-cellular trafficking biology.organism_classification 3. Good health Cell biology 030104 developmental biology Cytoplasm 030220 oncology & carcinogenesis General Agricultural and Biological Sciences Intracellular Research Article |
| Zdroj: | Biology Open, Vol 6, Iss 4, Pp 481-488 (2017) Biology Open |
| ISSN: | 2046-6390 |
| Popis: | Earlier studies suggested that Mycobacterium tuberculosis (Mtb) proteins exported within the host macrophage play an essential role in tuberculosis pathogenesis. In fact, Mtb proteins interact with and deactivate key regulators of many macrophage functions such as phago-lysosome fusion and antigen presentation, resulting in the intracellular persistence of pathogenic mycobacteria. Cpn60.2 is an abundant Mtb chaperone protein, restricted to cell cytoplasm and surface, that was reported to be essential for bacterial growth. Here, we provide evidence that once Mtb is ingested by the macrophage, Cpn60.2 is able to detach from the bacterial surface and crosses the phagosomal membrane towards mitochondria organelles. Once there, Cpn60.2 interacts with host mortalin, a member of the HSP 70 gene family that contributes to apoptosis modulation. In this regard, we showed that Cpn60.2 blocks macrophage apoptosis, a phenotype that is reversed when cells are pretreated with a specific mortalin inhibitor. Our findings have extended the current knowledge of the Mtb Cpn60.2 functions to add a strong anti-apoptotic activity dependent on its interaction with mitochondrial mortalin, which otherwise promotes Mtb survival in the hostile macrophage environment. Summary: Once macrophage ingests Mycobacterium tuberculosis, the chaperone Cpn60.2 detaches from mycobacterial surface and traffics towards mitochondria. Once there, Cpn60.2 interacts with host mortalin leading to inhibition of macrophage's apoptosis. |
| Databáze: | OpenAIRE |
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