Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection

Visceral leishmaniasis (VL) is a vector-borne infectious disease that can be potentially fatal if left untreated. In Brazil, it is caused by Leishmania infantum parasites. Blood transcriptomics allows us to assess the molecular mechanisms involved in the immunopathological processes of several clini...

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Main Authors: Sandra Regina Maruyama, Carlos Alessandro Fuzo, Antonio Edson R. Oliveira, Luana Aparecida Rogerio, Nayore Tamie Takamiya, Gabriela Pessenda, Enaldo Vieira de Melo, Angela Maria da Silva, Amélia Ribeiro Jesus, Vanessa Carregaro, Helder I. Nakaya, Roque Pacheco Almeida, João Santana da Silva
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.784463/full
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author Sandra Regina Maruyama
Carlos Alessandro Fuzo
Antonio Edson R. Oliveira
Luana Aparecida Rogerio
Nayore Tamie Takamiya
Gabriela Pessenda
Enaldo Vieira de Melo
Angela Maria da Silva
Amélia Ribeiro Jesus
Vanessa Carregaro
Helder I. Nakaya
Roque Pacheco Almeida
João Santana da Silva
João Santana da Silva
author_facet Sandra Regina Maruyama
Carlos Alessandro Fuzo
Antonio Edson R. Oliveira
Luana Aparecida Rogerio
Nayore Tamie Takamiya
Gabriela Pessenda
Enaldo Vieira de Melo
Angela Maria da Silva
Amélia Ribeiro Jesus
Vanessa Carregaro
Helder I. Nakaya
Roque Pacheco Almeida
João Santana da Silva
João Santana da Silva
author_sort Sandra Regina Maruyama
collection DOAJ
description Visceral leishmaniasis (VL) is a vector-borne infectious disease that can be potentially fatal if left untreated. In Brazil, it is caused by Leishmania infantum parasites. Blood transcriptomics allows us to assess the molecular mechanisms involved in the immunopathological processes of several clinical conditions, namely, parasitic diseases. Here, we performed mRNA sequencing of peripheral blood from patients with visceral leishmaniasis during the active phase of the disease and six months after successful treatment, when the patients were considered clinically cured. To strengthen the study, the RNA-seq data analysis included two other non-diseased groups composed of healthy uninfected volunteers and asymptomatic individuals. We identified thousands of differentially expressed genes between VL patients and non-diseased groups. Overall, pathway analysis corroborated the importance of signaling involving interferons, chemokines, Toll-like receptors and the neutrophil response. Cellular deconvolution of gene expression profiles was able to discriminate cellular subtypes, highlighting the contribution of plasma cells and NK cells in the course of the disease. Beyond the biological processes involved in the immunopathology of VL revealed by the expression of protein coding genes (PCGs), we observed a significant participation of long noncoding RNAs (lncRNAs) in our blood transcriptome dataset. Genome-wide analysis of lncRNAs expression in VL has never been performed. lncRNAs have been considered key regulators of disease progression, mainly in cancers; however, their pattern regulation may also help to understand the complexity and heterogeneity of host immune responses elicited by L. infantum infections in humans. Among our findings, we identified lncRNAs such as IL21-AS1, MIR4435-2HG and LINC01501 and coexpressed lncRNA/mRNA pairs such as CA3-AS1/CA1, GASAL1/IFNG and LINC01127/IL1R1-IL1R2. Thus, for the first time, we present an integrated analysis of PCGs and lncRNAs by exploring the lncRNA–mRNA coexpression profile of VL to provide insights into the regulatory gene network involved in the development of this inflammatory and infectious disease.
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spelling doaj.art-21160203167f47ab8feb37c1c96d7ce72022-12-21T18:20:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-03-011310.3389/fimmu.2022.784463784463Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum InfectionSandra Regina Maruyama0Carlos Alessandro Fuzo1Antonio Edson R. Oliveira2Luana Aparecida Rogerio3Nayore Tamie Takamiya4Gabriela Pessenda5Enaldo Vieira de Melo6Angela Maria da Silva7Amélia Ribeiro Jesus8Vanessa Carregaro9Helder I. Nakaya10Roque Pacheco Almeida11João Santana da Silva12João Santana da Silva13Department of Genetics and Evolution, Center for Biological Sciences and Health, Federal University of São Carlos, São Carlos, BrazilDepartment of Clinical Analyses, Toxicology and Food Sciences, Ribeirão Preto School of Pharmaceutics Sciences, University of São Paulo, Ribeirão Preto, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Genetics and Evolution, Center for Biological Sciences and Health, Federal University of São Carlos, São Carlos, BrazilDepartment of Genetics and Evolution, Center for Biological Sciences and Health, Federal University of São Carlos, São Carlos, BrazilDepartment of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilDepartment of Medicine, University Hospital-Empresa Brasileira de Serviços Hospitalares (EBSERH), Federal University of Sergipe, Aracaju, BrazilDepartment of Medicine, University Hospital-Empresa Brasileira de Serviços Hospitalares (EBSERH), Federal University of Sergipe, Aracaju, BrazilDepartment of Medicine, University Hospital-Empresa Brasileira de Serviços Hospitalares (EBSERH), Federal University of Sergipe, Aracaju, BrazilDepartment of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilHospital Israelita Albert Einstein, São Paulo, BrazilDepartment of Medicine, University Hospital-Empresa Brasileira de Serviços Hospitalares (EBSERH), Federal University of Sergipe, Aracaju, BrazilDepartment of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilFiocruz-Bi-Institutional Translational Medicine Platform, Ribeirão Preto, BrazilVisceral leishmaniasis (VL) is a vector-borne infectious disease that can be potentially fatal if left untreated. In Brazil, it is caused by Leishmania infantum parasites. Blood transcriptomics allows us to assess the molecular mechanisms involved in the immunopathological processes of several clinical conditions, namely, parasitic diseases. Here, we performed mRNA sequencing of peripheral blood from patients with visceral leishmaniasis during the active phase of the disease and six months after successful treatment, when the patients were considered clinically cured. To strengthen the study, the RNA-seq data analysis included two other non-diseased groups composed of healthy uninfected volunteers and asymptomatic individuals. We identified thousands of differentially expressed genes between VL patients and non-diseased groups. Overall, pathway analysis corroborated the importance of signaling involving interferons, chemokines, Toll-like receptors and the neutrophil response. Cellular deconvolution of gene expression profiles was able to discriminate cellular subtypes, highlighting the contribution of plasma cells and NK cells in the course of the disease. Beyond the biological processes involved in the immunopathology of VL revealed by the expression of protein coding genes (PCGs), we observed a significant participation of long noncoding RNAs (lncRNAs) in our blood transcriptome dataset. Genome-wide analysis of lncRNAs expression in VL has never been performed. lncRNAs have been considered key regulators of disease progression, mainly in cancers; however, their pattern regulation may also help to understand the complexity and heterogeneity of host immune responses elicited by L. infantum infections in humans. Among our findings, we identified lncRNAs such as IL21-AS1, MIR4435-2HG and LINC01501 and coexpressed lncRNA/mRNA pairs such as CA3-AS1/CA1, GASAL1/IFNG and LINC01127/IL1R1-IL1R2. Thus, for the first time, we present an integrated analysis of PCGs and lncRNAs by exploring the lncRNA–mRNA coexpression profile of VL to provide insights into the regulatory gene network involved in the development of this inflammatory and infectious disease.https://www.frontiersin.org/articles/10.3389/fimmu.2022.784463/fullblood transcriptomicshuman visceral leishmaniasisLeishmania infantum (syn. Leishmania chagasi)mRNA sequencing (mRNA-seq)long noncoding RNA–mRNA coexpression
spellingShingle Sandra Regina Maruyama
Carlos Alessandro Fuzo
Antonio Edson R. Oliveira
Luana Aparecida Rogerio
Nayore Tamie Takamiya
Gabriela Pessenda
Enaldo Vieira de Melo
Angela Maria da Silva
Amélia Ribeiro Jesus
Vanessa Carregaro
Helder I. Nakaya
Roque Pacheco Almeida
João Santana da Silva
João Santana da Silva
Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection
Frontiers in Immunology
blood transcriptomics
human visceral leishmaniasis
Leishmania infantum (syn. Leishmania chagasi)
mRNA sequencing (mRNA-seq)
long noncoding RNA–mRNA coexpression
title Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection
title_full Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection
title_fullStr Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection
title_full_unstemmed Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection
title_short Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection
title_sort insight into the long noncoding rna and mrna coexpression profile in the human blood transcriptome upon leishmania infantum infection
topic blood transcriptomics
human visceral leishmaniasis
Leishmania infantum (syn. Leishmania chagasi)
mRNA sequencing (mRNA-seq)
long noncoding RNA–mRNA coexpression
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.784463/full
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