Dual RNAseq of human leprosy lesions identifies bacterial determinants linked to host immune response

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. We performed dual RNAseq on patient lesions, identifying a continuum of distinct bacterial states that are linked to the host immune response. The bacterial burden, represented by the fraction of bacterial transcripts, correlates with a host type I IFN gene signature, known to inhibit antimicrobial responses. Second, the bacterial transcriptional activity, defined by the bacterial mRNA/rRNA ratio, links bacterial heat shock proteins with the BAFF-BCMA host antibody response pathway. Our findings provide a platform for interrogation of host and pathogen transcriptomes at the site of infection, allowing insight into mechanisms of inflammation in human disease Overall design: RNA sequencing was performed on the total RNA from 24 leprosy skin biopsy specimens (9 L-lep, 6 T-lep, 9 RR). Microbeads with consensus sequences to human and bacterial ribosomal RNA (rRNA) were utilized for depletion. The enriched mRNA was then converted into sequencing libraries by random hexamer priming, sequenced via standard Illumina protocol, and mapped to both the human and M. leprae genomes