TY - JOUR KW - leprosy KW - Dual RNAseq KW - Bacterial determinants KW - Host immune response AU - Montoya DJ AU - Andrade P AU - Silva B AU - Teles R AU - Bryson B AU - Sadanand S AU - Noel T AU - Lu J AU - Sarno E AU - Arnvig K AU - Young D AU - Lahiri R AU - Williams DL AU - Fortune S AU - Bloom B AU - Pellegrini M AU - Modlin RL AB -

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.

BT - bioRxiv.org : the preprint server for biology J2 - bioRxivorg LA - eng N2 -

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.

PY - 2018 EP - 35 T2 - bioRxiv.org : the preprint server for biology TI - Dual RNAseq of human leprosy lesions identifies bacterial determinants linked to host immune response. UR - https://www.biorxiv.org/content/biorxiv/early/2018/06/22/354407.full.pdf ER -