2.50
Hdl Handle:
http://hdl.handle.net/10033/620582
Title:
Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis.
Authors:
Lerner, Thomas R; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R G; Borel, Sophie; Diedrich, Collin R; Rohde, M; Wainwright, Helen; Collinson, Lucy M; Wilkinson, Robert J; Griffiths, Gareth; Gutierrez, Maximiliano G
Abstract:
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.
Affiliation:
Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland Universitätscampus E8.1, 66123 Saarbrücken, Germany.
Citation:
Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis. 2016, 126 (3):1093-108 J. Clin. Invest.
Journal:
The Journal of clinical investigation
Issue Date:
1-Mar-2016
URI:
http://hdl.handle.net/10033/620582
DOI:
10.1172/JCI83379
PubMed ID:
26901813
Type:
Article
ISSN:
1558-8238
Appears in Collections:
publications of the department drug delivery ([TC] DDEL)

Full metadata record

DC FieldValue Language
dc.contributor.authorLerner, Thomas Ren
dc.contributor.authorde Souza Carvalho-Wodarz, Cristianeen
dc.contributor.authorRepnik, Urskaen
dc.contributor.authorRussell, Matthew R Gen
dc.contributor.authorBorel, Sophieen
dc.contributor.authorDiedrich, Collin Ren
dc.contributor.authorRohde, Men
dc.contributor.authorWainwright, Helenen
dc.contributor.authorCollinson, Lucy Men
dc.contributor.authorWilkinson, Robert Jen
dc.contributor.authorGriffiths, Garethen
dc.contributor.authorGutierrez, Maximiliano Gen
dc.date.accessioned2016-11-17T08:52:31Z-
dc.date.available2016-11-17T08:52:31Z-
dc.date.issued2016-03-01-
dc.identifier.citationLymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis. 2016, 126 (3):1093-108 J. Clin. Invest.en
dc.identifier.issn1558-8238-
dc.identifier.pmid26901813-
dc.identifier.doi10.1172/JCI83379-
dc.identifier.urihttp://hdl.handle.net/10033/620582-
dc.description.abstractIn 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.en
dc.languageENG-
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/289454en
dc.rightsopenAccessen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAutophagyen
dc.subject.meshCells, Cultureden
dc.subject.meshEndothelial Cellsen
dc.subject.meshGranulomaen
dc.subject.meshHumansen
dc.subject.meshLymph Nodesen
dc.subject.meshMycobacterium tuberculosisen
dc.subject.meshNitric Oxideen
dc.subject.meshTuberculosisen
dc.titleLymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis.
dc.typeArticleen
dc.contributor.departmentHelmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland Universitätscampus E8.1, 66123 Saarbrücken, Germany.en
dc.identifier.journalThe Journal of clinical investigationen

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