Article
Dual RNA-Seq of Human Leprosy Lesions Identifies Bacterial Determinants Linked to Host Immune Response
Registro en:
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.
2211-1247
10.1016/j.celrep.2019.02.109
2211-1247
Autor
Montoya, Dennis J.
Andrade, Priscila
Silva, Bruno J. A.
Teles, Rosane M. B.
Ma, Feiyang
Bryson, Bryan
Sadanand, Saheli
Noel, Teia
Lu, Jing
Sarno, Euzenir N.
Arnvig, Kristine B.
Young, Douglas
Lahiri, Ramanuj
Williams, Diana L.
Fortune, Sarah
Bloom, Barry R.
Pellegrini, Matteo
Modlin, Robert L.
Resumen
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.