Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/14782
Title: STING-Dependent 2′-5′ Oligoadenylate Synthetase–Like Production Is Required for Intracellular Mycobacterium leprae Survival
Authors: Pinto, Thiago Gomes de Toledo
Ferreira, Anna Beatriz Robottom
Alves, Marcelo Ribeiro
Rodrigues, Luciana Silva
Silva, Leonardo Ribeiro Batista
Silva, Bruno Jorge de Andrade
Lemes, Robertha Mariana Rodrigues
Martinez, Alejandra Nóbrega
Sandoval, Felipe Galvan
Alvarado-Arnez, Lucia Elena
Rosa, Patrícia Sammarco
Shannon, Edward Joseph
Pessolani, Maria Cristina Vidal
Pinheiro, Roberta Olmo
Antunes, Sérgio Luís Gomes
Sarno, Euzenir Nunes
Lara, Flávio Alves
Williams, Diana Lynn
Moraes, Milton Ozório
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Laboratório de Pesquisa em Farmacogenética. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Pavilhão de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Pavilhão de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
National Hansen’s Disease Programs. Bureau of Primary Health Care. Health Resources and Services Administration. Baton Rouge, USA / Louisiana State University. School of Veterinary Medicine. Laboratory Research Branch. Baton Rouge, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Instituto Lauro de Souza Lima. Bauru, SP, Brasil.
National Hansen’s Disease Programs. Bureau of Primary Health Care. Health Resources and Services Administration. Baton Rouge, USA / Louisiana State University. School of Veterinary Medicine. Laboratory Research Branch. Baton Rouge, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Pavilhão de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Pavilhão de Hanseníase. Rio de Janeiro, RJ, Brasil.
National Hansen’s Disease Programs. Bureau of Primary Health Care. Health Resources and Services Administration. Baton Rouge, USA / Louisiana State University. School of Veterinary Medicine. Laboratory Research Branch. Baton Rouge, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Abstract: Cytosolic detection of nucleic acids elicits a type I interferon (IFN) response and plays a critical role in host defense against intracellular pathogens. Herein, a global gene expression profile of Mycobacterium leprae-infected primary human Schwann cells identified the genes differentially expressed in the type I IFN pathway. Among them, the gene encoding 2'-5' oligoadenylate synthetase-like (OASL) underwent the greatest upregulation and was also shown to be upregulated in M. leprae-infected human macrophage cell lineages, primary monocytes, and skin lesion specimens from patients with a disseminated form of leprosy. OASL knock down was associated with decreased viability of M. leprae that was concomitant with upregulation of either antimicrobial peptide expression or autophagy levels. Downregulation of MCP-1/CCL2 release was also observed during OASL knock down. M. leprae-mediated OASL expression was dependent on cytosolic DNA sensing mediated by stimulator of IFN genes signaling. The addition of M. leprae DNA enhanced nonpathogenic Mycobacterium bovis bacillus Calmette-Guerin intracellular survival, downregulated antimicrobial peptide expression, and increased MCP-1/CCL2 secretion. Thus, our data uncover a promycobacterial role for OASL during M. leprae infection that directs the host immune response toward a niche that permits survival of the pathogen.
Keywords: Leprosy
type I IFN
OASL
Mycobacterium leprae
cytoplasmic DNA sensing
Autophagy
keywords: Hanseníase
Mycobacterium leprae
Sensor de DNA citoplasmático
Autofagia
Interferon Tipo I
Issue Date: 2016
Publisher: Oxford University Press
Citation: PINTO, Thiago Gomes de Toledo; et al. STING-Dependent 2′-5′ Oligoadenylate Synthetase–Like Production Is Required for Intracellular Mycobacterium leprae Survival. The Journal od Infectious Diseases, v.214, n.2, p.311-20, July 2016.
DOI: 10.1093/infdis/jiw144
ISSN: 1537-6613
Copyright: restricted access
Appears in Collections:INI - Artigos de Periódicos
IOC - Artigos de Periódicos

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