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

University of California Los Angeles. Department of Molecular, Cell, and Developmental Biology. Los Angeles, CA, USA.
David Geffen School of Medicine. Division of Dermatology. Los Angeles, CA, USA.
David Geffen School of Medicine. Division of Dermatology. Los Angeles, CA, USA.
David Geffen School of Medicine. Division of Dermatology. Los Angeles, CA, USA.
University of California Los Angeles. Department of Molecular, Cell, and Developmental Biology. Los Angeles, CA, USA.
Harvard T.H. Chan School of Public Health. Department of Immunology and Infectious Diseases. Boston, MA, USA.
Ragon Institute of MGH, MIT and Harvard. Cambridge, MA, USA.
University of California Los Angeles. Department of Molecular, Cell, and Developmental Biology. Los Angeles, CA, USA.
University of California Los Angeles. Department of Molecular, Cell, and Developmental Biology. Los Angeles, CA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Micobacterioses. Rio de Janeiro, RJ, Brasil.
University College London. Institute for Structural and Molecular Biology. London, UK.
National Institute for Medical Research. Mycobacterial Research Division. London, UK / The Francis Crick Institute. Mill Hill Laboratory. The Ridgeway. London, USA.
Health Resources and Services Administration. National Hansen’s Disease Program. Baton Rouge, LA, USA.
Health Resources and Services Administration. National Hansen’s Disease Program. Baton Rouge, LA, USA / Louisiana State University. Department of Pathobiological Sciences. Baton Rouge, LA, USA.
Harvard T.H. Chan School of Public Health. Department of Immunology and Infectious Diseases. Boston, MA, USA.
Harvard T.H. Chan School of Public Health. Department of Immunology and Infectious Diseases. Boston, MA, USA.
University of California Los Angeles. Department of Molecular, Cell, and Developmental Biology. Los Angeles, CA, USA.
David Geffen School of Medicine. Division of Dermatology. Los Angeles, CA, USA.

Abstract

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.

Keywords in Portuguese

Hanseníase humana
RNA-Seq duplo
Determinantes bacterianos
Resposta imune do hospedeiro
Mycobacterium leprae

Keywords

Human Leprosy
Bacterial Determinants
Host Immune Response
Dual RNA-Seq
Mycobacterium leprae

Publisher

Elsevier

Citation

MONTOYA, Dennis J. et al. Dual RNA-Seq of Human Leprosy Lesions Identifies Bacterial Determinants Linked to Host Immune Response. Cell Reports, v. 26, n. 13, p. 3574-3585, Mar. 2019.

DOI

10.1016/j.celrep.2019.02.109

ISSN

2211-1247

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/35255

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Open access

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