01932nas a2200349   4500000000100000008004100001653001200042653001600054653002700070653002500097100001500122700001400137700001200151700001200163700001300175700001500188700001100203700000900214700001200223700001300235700001200248700001300260700001600273700001400289700001200303700001700315700001400332245010700346856007700453300000700530520104500537       2018                            d10aleprosy10aDual RNAseq10aBacterial determinants10aHost immune response1 aMontoya DJ1 aAndrade P1 aSilva B1 aTeles R1 aBryson B1 aSadanand S1 aNoel T1 aLu J1 aSarno E1 aArnvig K1 aYoung D1 aLahiri R1 aWilliams DL1 aFortune S1 aBloom B1 aPellegrini M1 aModlin RL00aDual RNAseq of human leprosy lesions identifies bacterial determinants linked to host immune response.  uhttps://www.biorxiv.org/content/biorxiv/early/2018/06/22/354407.full.pdf  a353 a<p>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.</p>