Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis.
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Authors
Lerner, Thomas Rde 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
Issue Date
2016-03-01
Metadata
Show full item recordAbstract
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.Citation
Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis. 2016, 126 (3):1093-108 J. Clin. Invest.Affiliation
Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland Universitätscampus E8.1, 66123 Saarbrücken, Germany.DOI
10.1172/JCI83379PubMed ID
26901813Type
ArticleISSN
1558-8238ae974a485f413a2113503eed53cd6c53
10.1172/JCI83379
Scopus Count
The following license files are associated with this item:
- Creative Commons
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