Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis
| العنوان: | Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis |
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| المؤلفون: | Urska Repnik, Maximiliano G. Gutierrez, Sophie Borel, Manfred Rohde, Collin R. Diedrich, Gareth Griffiths, Helen Wainwright, Thomas R. Lerner, Matthew R. G. Russell, Cristiane de Souza Carvalho-Wodarz, Lucy M. Collinson, Robert J. Wilkinson |
| المساهمون: | Wellcome Trust, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland Universitätscampus E8.1, 66123 Saarbrücken, Germany. |
| المصدر: | Journal of Clinical Investigation. 126:1093-1108 |
| بيانات النشر: | American Society for Clinical Investigation, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Research & Experimental Medicine, Pathogenesis, ATTENUATION, INFECTION, VASCULATURE, IMMUNE-RESPONSE, Cells, Cultured, Granuloma, 11 Medical And Health Sciences, General Medicine, 3. Good health, Lymphatic Endothelium, Lymphatic system, Medicine, Research & Experimental, AUTOPHAGY, Lymph, Life Sciences & Biomedicine, Research Article, GRANULOMAS, Tuberculosis, government.form_of_government, Immunology, Biology, Nitric Oxide, Mycobacterium tuberculosis, 03 medical and health sciences, Immune system, Autophagy, medicine, Humans, TRAFFICKING, NITRIC-OXIDE SYNTHASE, Science & Technology, INTERFERON-GAMMA, fungi, Endothelial Cells, medicine.disease, biology.organism_classification, 030104 developmental biology, CALMETTE-GUERIN, Cancer research, government, Lymph Nodes, sense organs |
| الوصف: | In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. |
| تدمد: | 1558-8238 0021-9738 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::266d4f6901b3c938c1d06a7390fc84bdTest https://doi.org/10.1172/jci83379Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....266d4f6901b3c938c1d06a7390fc84bd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15588238 00219738 |
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