Montoya, DJ;
Andrade, P;
Silva, BJA;
Teles, RMB;
Ma, F;
Bryson, B;
Sadanand, S;
... Modlin, RL; + view all
(2019)
Dual RNA-Seq of Human Leprosy Lesions Identifies Bacterial Determinants Linked to Host Immune Response.
Cell Reports
, 26
(13)
3574-3585.e3.
10.1016/j.celrep.2019.02.109.
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Abstract
Summary To understand how the interaction between an intracellular bacterium and the host immune system contributes to outcome at the site of infection, we studied leprosy, a disease that forms a clinical spectrum, in which progressive infection by the intracellular bacterium Mycobacterium leprae is characterized by the production of type I IFNs and antibody production. Dual RNA-seq on patient lesions identifies two independent molecular measures of M. leprae, each of which correlates with distinct aspects of the host immune response. The fraction of bacterial transcripts, reflecting bacterial burden, correlates with a host type I IFN gene signature, known to inhibit antimicrobial responses. Second, the bacterial mRNA:rRNA ratio, reflecting bacterial viability, links bacterial heat shock proteins with the BAFF-BCMA host antibody response pathway. Our findings provide a platform for the interrogation of host and pathogen transcriptomes at the site of infection, allowing insight into mechanisms of inflammation in human disease.
Type: | Article |
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Title: | Dual RNA-Seq of Human Leprosy Lesions Identifies Bacterial Determinants Linked to Host Immune Response |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.celrep.2019.02.109 |
Publisher version: | https://doi.org/10.1016/j.celrep.2019.02.109 |
Language: | English |
Additional information: | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/ |
Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, I INTERFERON, TUBERCULOSIS, ANTIBODIES, VIABILITY, PROTEINS, VACCINATION, INFECTION, EFFICACY, PATHWAY, TARGETS |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10075444 |
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