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

Abstract

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.

More information

Type
Journal Article
Author
R Andrade P
Mehta M
Lu J
M B Teles R
Montoya D
O Scumpia P
Nunes Sarno E
Ochoa MT
Ma F
Pellegrini M
Modlin RL
Year of Publication
2019
Journal
PLoS neglected tropical diseases
Volume
13
Issue
7
Number of Pages
e0007589
Language
eng
ISSN Number
1935-2735
DOI
10.1371/journal.pntd.0007589
Alternate Journal
PLoS Negl Trop Dis
Publication Language
eng