Open AccessThe cell fate regulator NUPR1 is induced by Mycobacterium leprae via type I interferon in human leprosy
Author(s) -
Priscila Ribeiro Andrade,
Manali Mehta,
Jing Lü,
Rosane M. B. Teles,
Dennis Montoya,
Phillip Scumpia,
Euzenir Nunes Sarno,
María Teresa Ochoa,
Feiyang Ma,
Matteo Pellegrini,
Robert L. Modlin
Publication year - 2019
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0007589
Subject(s) - mycobacterium leprae , biology , immune system , interferon , transcriptome , intracellular parasite , immunology , leprosy , pathogen , innate immune system , microbiology and biotechnology , regulator , gene , gene expression , genetics
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.