title: STING-Dependent 2'-5' Oligoadenylate Synthetase-Like Production Is Required for Intracellular Mycobacterium leprae Survival.
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.
authors.affiliation: Laboratório de Hanseníase.
authors.forename: Thiago Gomes
authors.initials: TG
authors.lastname: de Toledo-Pinto
authors.affiliation: Laboratório de Hanseníase.
authors.forename: Anna Beatriz Robottom
authors.initials: AB
authors.lastname: Ferreira
authors.affiliation: Laboratório de Hanseníase Laboratório de Pesquisa em Farmacogenética, Instituto de Pesquisa Clínica Evandro Chagas, FIOCRUZ-RJ, Rio de Janeiro.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ribeiro-Alves
authors.affiliation: Laboratório de Microbiologia Celular, Pavilhão de Hanseníase, Instituto Oswaldo Cruz, FIOCRUZ.
authors.forename: Luciana Silva
authors.initials: LS
authors.lastname: Rodrigues
authors.affiliation: Laboratório de Hanseníase.
authors.forename: Leonardo Ribeiro
authors.initials: LR
authors.lastname: Batista-Silva
authors.affiliation: Laboratório de Hanseníase.
authors.forename: Bruno Jorge de Andrade
authors.initials: BJ
authors.lastname: Silva
authors.affiliation: Laboratório de Microbiologia Celular, Pavilhão de Hanseníase, Instituto Oswaldo Cruz, FIOCRUZ.
authors.forename: Robertha Mariana Rodrigues
authors.initials: RM
authors.lastname: Lemes
authors.affiliation: Laboratório de Hanseníase.
authors.forename: Alejandra Nóbrega
authors.initials: AN
authors.lastname: Martinez
authors.affiliation: National Hansen's Disease Programs, Bureau of Primary Health Care, Health Resources and Services Administration Laboratory Research Branch, School of Veterinary Medicine, Louisiana State University, Baton Rouge.
authors.forename: Felipe Galvan
authors.initials: FG
authors.lastname: Sandoval
authors.affiliation: Laboratório de Hanseníase.
authors.forename: Lucia Elena
authors.initials: LE
authors.lastname: Alvarado-Arnez
authors.affiliation: Instituto Lauro de Souza Lima, Bauru, Brazil.
authors.forename: Patrícia Sammarco
authors.initials: PS
authors.lastname: Rosa
authors.affiliation: National Hansen's Disease Programs, Bureau of Primary Health Care, Health Resources and Services Administration Laboratory Research Branch, School of Veterinary Medicine, Louisiana State University, Baton Rouge.
authors.forename: Edward Joseph
authors.initials: EJ
authors.lastname: Shannon
authors.affiliation: Laboratório de Microbiologia Celular, Pavilhão de Hanseníase, Instituto Oswaldo Cruz, FIOCRUZ.
authors.forename: Maria Cristina Vidal
authors.initials: MC
authors.lastname: Pessolani
authors.affiliation: Laboratório de Hanseníase.
authors.forename: Roberta Olmo
authors.initials: RO
authors.lastname: Pinheiro
authors.affiliation: Laboratório de Hanseníase.
authors.forename: Sérgio Luís Gomes
authors.initials: SL
authors.lastname: Antunes
authors.affiliation: Laboratório de Hanseníase.
authors.forename: Euzenir Nunes
authors.initials: EN
authors.lastname: Sarno
authors.affiliation: Laboratório de Microbiologia Celular, Pavilhão de Hanseníase, Instituto Oswaldo Cruz, FIOCRUZ.
authors.forename: Flávio Alves
authors.initials: FA
authors.lastname: Lara
authors.affiliation: National Hansen's Disease Programs, Bureau of Primary Health Care, Health Resources and Services Administration Laboratory Research Branch, School of Veterinary Medicine, Louisiana State University, Baton Rouge.
authors.forename: Diana Lynn
authors.initials: DL
authors.lastname: Williams
authors.affiliation: Laboratório de Hanseníase.
authors.forename: Milton
authors.initials: M
authors.lastname: Ozório Moraes
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D007918:Leprosy / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000382:microbiology; D008565:Membrane Proteins / Q000378:metabolism*; D050296:Microbial Viability; D009163:Mycobacterium bovis / Q000502:physiology; D009166:Mycobacterium leprae / Q000502:physiology*; D012583:Schwann Cells / Q000382:microbiology*; D000099197:STING Protein
chemical_list: D015088:2',5'-Oligoadenylate Synthetase; D008565:Membrane Proteins; C532857:STING1 protein, human; D000099197:STING Protein; C115020:OASL protein, human
keywords: Mycobacterium leprae; OASL; autophagy; cytoplasmic DNA sensing; leprosy; type I IFN