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.

• Authors: Priscila R Andrade, Manali Mehta, Jing Lu, Rosane M B Teles, Dennis Montoya, Phillip O Scumpia, Euzenir Nunes Sarno, Maria Teresa Ochoa, Feiyang Ma, Matteo Pellegrini, Robert L Modlin
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 13 Issue 7 Pg. e0007589 (07 2019) ISSN: 1935-2735 [Electronic] United States
• PMID: 31344041 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Interferon Type I
• NUPR1 protein, human
• Neoplasm Proteins

Topics

• Basic Helix-Loop-Helix Transcription Factors (genetics)
• Cells, Cultured
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• Interferon Type I (immunology)
• Leprosy (genetics, immunology, microbiology)
• Macrophages (immunology, microbiology)
• Mycobacterium leprae (immunology)
• Neoplasm Proteins (genetics)
• Signal Transduction