A Rab20-Dependent Membrane Trafficking Pathway Controls M. tuberculosis Replication by Regulating Phagosome Spaciousness and Integrity
| العنوان: | A Rab20-Dependent Membrane Trafficking Pathway Controls M. tuberculosis Replication by Regulating Phagosome Spaciousness and Integrity |
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| المؤلفون: | Urska Repnik, Maximiliano G. Gutierrez, Robert J. Wilkinson, Laura Schnettger, Angela Rodgers, Martijn Verdoes, Gang Pei, Douglas Young, Rachel P. J. Lai |
| المساهمون: | Wellcome Trust |
| المصدر: | Cell Host & Microbe Cell Host & Microbe, 21, 5, pp. 619-628 e5 Cell Host & Microbe, 21, 619-628 e5 628.e5 |
| بيانات النشر: | Cell Press, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell Culture Techniques, mycobacterium, Mice, 1108 Medical Microbiology, Phagosomes, INFECTION, Macrophage, IN-VIVO, Phagosome, Rab GTPases, respiratory system, phagosome, 3. Good health, Cell biology, Protein Transport, tuberculosis, Host-Pathogen Interactions, AUTOPHAGY, Female, MYCOBACTERIUM-TUBERCULOSIS, Life Sciences & Biomedicine, 0605 Microbiology, Tuberculosis, 030106 microbiology, Immunology, chemical and pharmacologic phenomena, INNATE, macrophage, Endosomes, Biology, Microbiology, DENDRITIC CELLS, MATURATION, Mycobacterium tuberculosis, 03 medical and health sciences, Interferon-gamma, Short Article, Spatio-Temporal Analysis, Downregulation and upregulation, Bacterial Proteins, Virology, Organelle, medicine, Rab20, Animals, Humans, Antigens, Bacterial, Science & Technology, Membranes, Sequence Analysis, RNA, Macrophages, Sputum, DEGRADATION, medicine.disease, biology.organism_classification, bacterial infections and mycoses, Mice, Inbred C57BL, Cytosol, Disease Models, Animal, 030104 developmental biology, RAW 264.7 Cells, rab GTP-Binding Proteins, VIRULENCE, Parasitology, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Mycobacterium |
| الوصف: | Summary The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. The host pathways and mechanisms that contribute to maintaining Mtb phagosome integrity have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb-containing phagosomes and identified an interferon-gamma-stimulated and Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes. This pathway functions to promote endosomal membrane influx in infected macrophages, and is required to preserve Mtb phagosome integrity and control Mtb replication. Rab20 is specifically and significantly upregulated in the sputum of human patients with active tuberculosis. Altogether, we uncover an immune-regulated cellular pathway of defense that promotes maintenance of Mtb within intact membrane-bound compartments for efficient elimination. Graphical Abstract Highlights • The spatiotemporal dynamics of the M. tuberculosis (Mtb) phagosome were investigated • A Rab20-dependent pathway regulates endocytic influx into Mtb phagosomes • Mtb avoids targeting to Rab20-positive phagosomes through its ESX-1 system • Rab20 is required to maintain Mtb phagosome integrity and for control of Mtb replication Host-dependent mechanisms that regulate the M. tuberculosis (Mtb) phagosome are unexplored. Schnettger et al. investigate the spatiotemporal dynamics of Mtb phagosomes and identify an IFN-γ-stimulated, Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes and is required for mycobacterial control. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1934-6069 1931-3128 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2d5cccdccc4ce15d398c3fcf085392e1Test http://europepmc.org/articles/PMC5432432Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2d5cccdccc4ce15d398c3fcf085392e1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19346069 19313128 |
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