Journal Article

The cell fate regulator NUPR1 is induced by Mycobacterium leprae via type I interferon in human leprosy

R. Andrade, Priscila, Mehta, Manali, Ochoa, Maria Teresa, Montoya, Dennis, Ma, Feiyang, Lu, Jing, O. Scumpia, Phillip, Nunes Sarno, Euzenir, M. B. Teles, Rosane, Pellegrini, Matteo, Modlin, Robert L.

2019

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Apoptosis / Autophagy / Bacteria / Basic Helix-Loop-Helix Transcription Factors - genetics / Biological response modifiers / Biology and Life Sciences / Care and treatment / Cell death / Cell fate / Cells, Cultured / Cellular proteins / Cytokines / Defence mechanisms / Dermatology / Development and progression / Developmental biology / Geffen, David / Gene expression / Gene Expression Profiling / Gene Expression Regulation / Genes / Genetic aspects / Health aspects / Host-bacteria relationships / Human behavior / Humans / Immune response / Immune response regulation / Immune system / Immunity / Infection / Infections / Interferon / Interferon Type I - immunology / Introduced species / Leprosy / Leprosy - genetics / Leprosy - immunology / Leprosy - microbiology / Lesions / Macrophages / Macrophages - immunology / Macrophages - microbiology / Medical research / Medicine / Medicine and Health Sciences / Messenger RNA / Microorganisms / Molecules / Mycobacterium leprae / Mycobacterium leprae - immunology / Neoplasm Proteins - genetics / Pathogens / Phagocytosis / RNA / Signal Transduction / Skin / Skin diseases / Tropical diseases / β-Interferon