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

University of California Los Angeles. David Geffen School of Medicine. Department of Dermatology. Los Angeles, CA, USA.
University of California Los Angeles. David Geffen School of Medicine. Department of Dermatology. Los Angeles, CA, USA
University of California Los Angeles. Department of Molecular, Cell, and Developmental Biology. Los Angeles, CA, USA.
University of California Los Angeles. David Geffen School of Medicine. Department of Dermatology. Los Angeles, CA, USA.
University of California Los Angeles. Department of Molecular, Cell, and Developmental Biology. Los Angeles, CA, USA.
University of California Los Angeles. David Geffen School of Medicine. Department of Dermatology. Los Angeles, CA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
University of Southern California School of Medicine. Department of Dermatology. Los Angeles, CA, USA.
University of California Los Angeles. Department of Molecular, Cell, and Developmental Biology. Los Angeles, CA, USA.
University of California Los Angeles. Department of Molecular, Cell, and Developmental Biology. Los Angeles, CA, USA.
University of California Los Angeles. David Geffen School of Medicine. Department of Dermatology. Los Angeles, CA, USA / University of California Los Angeles. Department of Microbiology, Immunology and Molecular Genetics. Los Angeles, CA, USA.

Resumo em Inglês

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.

Palavras-chave

Mycobacterium leprae
Regulador do destino celular
Interferon tipo I
Hanseníase humana
NUPR1

Palavras-chave em inglês

Mycobacterium leprae
T cell
Regulator NUPR1
Type I Interferon
Human leprosy

Editor

Public Library of Science

Referência

ANDRADE, Priscila R. et al. The cell fate regulator NUPR1 is induced by Mycobacterium leprae via type I interferon in human leprosy. PLoS Neglected Tropical Diseases, v. 13, n. 7, p. 1-18, July 2019.

DOI

10.1371/journal.pntd.0007589

ISSN

1935-2727

Use este identificador para citar ou linkar para este item: https://www.arca.fiocruz.br/handle/icict/35530

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Direito Autoral

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