title: MicroRNA expression signatures in lungs of mice infected with Mycobacterium tuberculosis.
abstract: Tuberculosis (TB) is a major public health concern worldwide; however the factors that account for resistance or susceptibility to disease are not completely understood. Although some studies suggest that the differential expression of miRNAs in peripheral blood of TB patients could be useful as biomarkers of active disease, their involvement during the inflammatory process in lungs of infected individuals is unknown. Here, we evaluated the global expression of miRNAs in the lungs of mice experimentally infected with Mycobacterium tuberculosis on 30 and 60 days post-infection. We observed that several miRNAs were differentially expressed compared to uninfected mice. Furthermore, we verified that the expression of miR-135b, miR-21, miR-155, miR-146a, and miR-146b was significantly altered in distinct leukocyte subsets isolated from lungs of infected mice, while genes potentially targeted by those miRNAs were associated with a diversity of immune related molecular pathways. Importantly, we validated the inhibition of Pellino 1 expression by miR-135b in vitro. Overall, this study contributes to the understanding of the dynamics of miRNA expression in lungs during experimental TB and adds further perspectives into the role of miRNAs on the regulation of immune processes such as leukocyte activation.
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: thiagomalardo@usp.br.
authors.forename: Thiago
authors.initials: T
authors.lastname: Malardo
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Luiz Gustavo
authors.initials: LG
authors.lastname: Gardinassi
authors.affiliation: Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Bernardo Pereira
authors.initials: BP
authors.lastname: Moreira
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Éverton
authors.initials: É
authors.lastname: Padilha
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Júlio César Cetrulo
authors.initials: JC
authors.lastname: Lorenzi
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Luana Silva
authors.initials: LS
authors.lastname: Soares
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Gembre
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Isabela Cardoso
authors.initials: IC
authors.lastname: Fontoura
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Luciana Previato
authors.initials: LP
authors.lastname: de Almeida
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Isabel Kinney Ferreira
authors.initials: IK
authors.lastname: de Miranda Santos
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Célio Lopes
authors.initials: CL
authors.lastname: Silva
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: accastel00@gmail.com.
authors.forename: Arlete Aparecida Martins
authors.initials: AA
authors.lastname: Coelho-Castelo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000276:immunology; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D059467:Transcriptome / Q000235:genetics* / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; C418046:Peli1 protein, mouse
keywords: MicroRNA; Microarray; Mycobacterium tuberculosis; Pellino 1; miR-135b