11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Brucellosis is a serious infectious disease that continues to be a significant cause of morbidity worldwide and across all ages. Despite early diagnosis and treatment, 10–30% of patients develop chronic brucellosis. Although there have been recent advances in our knowledge of Brucella virulence factors and hosts’ immune response to the infection, there is a lack of clear data regarding how the infection bypasses the immune system and becomes chronic. The present study investigated immunological factors and their roles in the transition of brucellosis from an acute to a chronic infection in CD4+ T cells. CD4+ T cells sorted from peripheral blood samples of patients with acute or chronic brucellosis and healthy controls using flow cytometry as well as more than 2000 miRNAs were screened using the GeneSpring GX (Agilent) 13.0 miRNA microarray software and were validated using reverse transcription polymerase chain reaction (RT-qPCR). Compared to acute cases, the expression levels of 28 miRNAs were significantly altered in chronic cases. Apart from one miRNA (miR-4649-3p), 27 miRNAs were not expressed in the acute cases (p <0.05, fold change> 2). According to KEGG pathway analysis, these miRNAs are involved in the regulation of target genes that were previously involved in the MAPK signalling pathway, regulation of the actin cytoskeleton, endocytosis, and protein processing in the endoplasmic reticulum. This indicates the potential role of these miRNAs in the development of chronic brucellosis. We suggest that these miRNAs can be used as markers to determine the transition of the disease into chronicity. This is the first study of miRNA expression that analyses human CD4+ T cells to clarify the mechanism of chronicity in brucellosis.

          Related collections

          Most cited references58

          • Record: found
          • Abstract: found
          • Article: not found

          Human brucellosis.

          Human brucellosis still presents scientists and clinicians with several challenges, such as the understanding of pathogenic mechanisms of Brucella spp, the identification of markers for disease severity, progression, and treatment response, and the development of improved treatment regimens. Molecular studies have shed new light on the pathogenesis of Brucella spp, and new technologies have permitted the development of diagnostic tools that will be useful in developing countries, where brucellosis is still a very common but often neglected disease. However, further studies are needed to establish optimum treatment regimens and local and international control programmes. This Review summarises current knowledge of the pathogenic mechanisms, new diagnostic advances, therapeutic options, and the situation of developing countries in regard to human brucellosis.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pathogenesis and immunobiology of brucellosis: review of Brucella-host interactions.

            This review of Brucella-host interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat brucellosis. Brucella spp., as animal pathogens, cause human brucellosis, a zoonosis that results in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, and no patient-friendly treatments or approved human vaccines are reported. Brucellae display strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifestyle that limits exposure to innate and adaptive immune responses, sequesters the organism from the effects of antibiotics, and drives clinical disease manifestations and pathology. Stealthy brucellae exploit strategies to establish infection, including i) evasion of intracellular destruction by restricting fusion of type IV secretion system-dependent Brucella-containing vacuoles with lysosomal compartments, ii) inhibition of apoptosis of infected mononuclear cells, and iii) prevention of dendritic cell maturation, antigen presentation, and activation of naive T cells, pathogenesis lessons that may be informative for other intracellular pathogens. Data sets of next-generation sequences of Brucella and host time-series global expression fused with proteomics and metabolomics data from in vitro and in vivo experiments now inform interactive cellular pathways and gene regulatory networks enabling full-scale systems biology analysis. The newly identified effector proteins of Brucella may represent targets for improved, safer brucellosis vaccines and therapeutics.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Inhibition of miR-25 Improves Cardiac Contractility in the Failing Heart

              Heart failure is characterized by a debilitating decline in cardiac function 1 , and recent clinical trial results indicate that improving the contractility of heart muscle cells by boosting intracellular calcium handling might be an effective therapy 2,3 . microRNAs (miRs) are dysregulated with heart failure 4,5 but whether they control contractility or constitute therapeutic targets remain speculative. Using high throughput, functional screening of the human microRNAome, we identified miRs that suppress intracellular calcium handling in heart muscle by interacting with mRNA encoding the sarcoplasmic reticulum calcium uptake pump SERCA2a. Of 875 miRs tested, miR-25 potently delayed calcium uptake kinetics in cardiomyocytes in vitro and was upregulated in heart failure, both in mice and humans. Whereas AAV9-mediated overexpression of miR-25 in vivo resulted in a significant loss of contractile function, injection of an antisense oligonucleotide (antagomiR) against miR-25 dramatically halted established heart failure in a mouse model, improving cardiac function and survival relative to a control antagomiR. These data reveal that increased expression of endogenous miR-25 contributes to declining cardiac function during heart failure and suggests that it might be targeted therapeutically to restore function.
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: Writing – original draft
                Role: InvestigationRole: Methodology
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: Writing – review & editing
                Role: Methodology
                Role: Methodology
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                13 June 2018
                2018
                : 13
                : 6
                : e0198659
                Affiliations
                [1 ] Department of Immunology, Faculty of Medicine, Uludag University, Bursa, Turkey
                [2 ] Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
                [3 ] Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Uludag University, Bursa, Turkey
                [4 ] Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
                East Carolina University Brody School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-7625-9148
                Article
                PONE-D-18-00800
                10.1371/journal.pone.0198659
                5999269
                29897958
                35a586ed-885e-4ce1-9b2d-470237d6004f
                © 2018 Budak et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 January 2018
                : 23 May 2018
                Page count
                Figures: 4, Tables: 4, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004410, Türkiye Bilimsel ve Teknolojik Araştirma Kurumu;
                Award ID: SBAG-111S183
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004410, Türkiye Bilimsel ve Teknolojik Araştirma Kurumu;
                Award ID: SBAG-111S183
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004410, Türkiye Bilimsel ve Teknolojik Araştirma Kurumu;
                Award ID: SBAG-111S183
                Award Recipient :
                Funded by: None
                Award Recipient :
                Funded by: None
                Award Recipient :
                Funded by: None
                Award Recipient :
                Funded by: None
                Award Recipient :
                Ferah Budak, Haluk Barbaros Oral, Emin Halis Akalın were the authors who were supported by a funder. They were supported by the the same grand. The name of the funder is: Türkiye Bilimsel ve Teknolojik Araştırma Kurumu. The link of the funder: ( https://www.tubitak.gov.tr). The grand number: SBAG-111S183. This funder (Türkiye Bilimsel ve Teknolojik Araştırma Kurumu) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The rest of the authors (Salih Haldun Bal, Gulcin Tezcan, Abdullah Yılmaz, Pınar Hız) were not supported by any funder.
                Categories
                Research Article
                Biology and life sciences
                Genetics
                Gene expression
                Gene regulation
                MicroRNAs
                Biology and life sciences
                Biochemistry
                Nucleic acids
                RNA
                Non-coding RNA
                MicroRNAs
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Brucellosis
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Brucellosis
                Medicine and Health Sciences
                Infectious Diseases
                Zoonoses
                Brucellosis
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                White Blood Cells
                T Cells
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Immune Cells
                White Blood Cells
                T Cells
                Biology and Life Sciences
                Immunology
                Immune Cells
                White Blood Cells
                T Cells
                Medicine and Health Sciences
                Immunology
                Immune Cells
                White Blood Cells
                T Cells
                Biology and Life Sciences
                Organisms
                Bacteria
                Brucella
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Brucella
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Bacterial Pathogens
                Brucella
                Biology and life sciences
                Cell biology
                Signal transduction
                Cell signaling
                Signaling cascades
                MAPK signaling cascades
                Biology and Life Sciences
                Genetics
                Gene Expression
                Gene Regulation
                Biology and Life Sciences
                Biochemistry
                Proteins
                Contractile Proteins
                Actins
                Biology and Life Sciences
                Biochemistry
                Proteins
                Cytoskeletal Proteins
                Actins
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Cytoskeleton
                Custom metadata
                The microarray data that support the findings of this study are deposited in the Gene Expression Omnibus with an accession number of GSE107554.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article