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Dual RNA-Seq of Human Leprosy Lesions Identifies Bacterial Determinants Linked to Host Immune Response

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. Green open access

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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
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.ucl.ac.uk/id/eprint/10075444
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