Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis
| Autor: | 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 |
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| Přispěvatelé: | Wellcome Trust, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland Universitätscampus E8.1, 66123 Saarbrücken, Germany. |
| Rok vydání: | 2016 |
| Předmět: |
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 |
| Zdroj: | Journal of Clinical Investigation. 126:1093-1108 |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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