01943nas a2200253 4500000000100000008004100001100001400042700001200056700000900068700001300077700001500090700001600105700001200121700001300133700000900146700001700155700001400172245010900186856007900295300001300374490000700387520128100394022001401675 2019 d1 aAndrade P1 aMehta M1 aLu J1 aTeles RM1 aMontoya DJ1 aO Scumpia P1 aSarno E1 aOchoa MT1 aMa F1 aPellegrini M1 aModlin RL00aThe cell fate regulator NUPR1 is induced by Mycobacterium leprae via type I interferon in human leprosy. uhttps://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0007589 ae00075890 v133 a
The initial interaction between a microbial pathogen and the host immune response influences the outcome of the battle between the host and the foreign invader. Leprosy, caused by the obligate intracellular pathogen Mycobacterium leprae, provides a model to study relevant human immune responses. Previous studies have adopted a targeted approach to investigate host response to M. leprae infection, focusing on the induction of specific molecules and pathways. By measuring the host transcriptome triggered by M. leprae infection of human macrophages, we were able to detect a host gene signature 24-48 hours after infection characterized by specific innate immune pathways involving the cell fate mechanisms autophagy and apoptosis. The top upstream regulator in the M. leprae-induced gene signature was NUPR1, which is found in the M. leprae-induced cell fate pathways. The induction of NUPR1 by M. leprae was dependent on the production of the type I interferon (IFN), IFN-β. Furthermore, NUPR1 mRNA and protein were upregulated in the skin lesions from patients with the multibacillary form of leprosy. Together, these data indicate that M. leprae induces a cell fate program which includes NUPR1 as part of the host response in the progressive form of leprosy.
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