Expression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of Malagasy subjects with tuberculosis
| Autor: | Lova H. Andriamihantasoa, Alimuddin Zumla, Jean-Louis Soares, Niaina Rakotosamimanana, Vincent Richard, T. Mark Doherty, Voahangy Rasolofo Razanamparany, Brigitte Gicquel |
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| Přispěvatelé: | Unité des Mycobactéries [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Statens Serum Institut [Copenhagen], Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris] (IP), Unité d'Epidémiologie [Antananarivo, Madagascar] (IPM), University College of London [London] (UCL), Institut Pasteur [Paris] |
| Rok vydání: | 2012 |
| Předmět: |
Male
Enzyme-Linked Immunospot Assay Endemic Diseases [SDV]Life Sciences [q-bio] CASP8 and FADD-Like Apoptosis Regulating Protein Apoptosis Monocytes Cohort Studies Leukocyte Count 0302 clinical medicine Interferon gamma Child Immune Response Regulation of gene expression 0303 health sciences Multidisciplinary biology T Cells ELISPOT Middle Aged Clinical Laboratory Sciences 3. Good health Host-Pathogen Interaction Infectious Diseases Child Preschool Cytokines Medicine Tumor necrosis factor alpha Female medicine.symptom medicine.drug Research Article Adult Tuberculosis Adolescent Clinical Research Design Science Immune Cells Immunology Asymptomatic Microbiology Mycobacterium tuberculosis 03 medical and health sciences Interferon-gamma Young Adult Bacterial Proteins Diagnostic Medicine medicine Madagascar Humans Receptors Tumor Necrosis Factor Type II Biology Immunity to Infections 030304 developmental biology Aged Antigens Bacterial business.industry Tuberculin Test Tumor Necrosis Factor-alpha Case-control study Immunity Tropical Diseases (Non-Neglected) biology.organism_classification medicine.disease Gene Expression Regulation Case-Control Studies Immune System business 030215 immunology Follow-Up Studies |
| Zdroj: | PLoS ONE PLoS ONE, 2013, 8 (4), pp.e61154. ⟨10.1371/journal.pone.0061154⟩ PLoS ONE, Public Library of Science, 2013, 8 (4), pp.e61154. ⟨10.1371/journal.pone.0061154⟩ PLoS ONE, Vol 8, Iss 4, p e61154 (2013) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0061154⟩ |
| Popis: | International audience; The majority of Mycobacterium tuberculosis (Mtb) infections remain asymptomatic with only up to 10% progressing to clinical tuberculosis. However, the constituents of the effective "protective immunity" against tuberculosis responsible for containing most infections remain unknown. Evaluating gene transcriptional profiles in tuberculosis clinical cohorts is one approach to understanding the spectrum of tuberculosis progression. It is clear that apoptosis plays a role in the control of tuberculosis but the utility of apoptosis-related genes as surrogate markers of protection against tuberculosis has not been well investigated. To characterize potential surrogate markers that could discriminate different phases of the clinical tuberculosis spectrum, we investigated gene expression of several TNF-alpha dependent apoptotic genes (TNFR1, TNFR2, FLICE, FLIPs) by real-time RT-PCR of peripheral blood cells from cohorts of individuals with active tuberculosis or potential exposure to tuberculosis. Newly diagnosed tuberculosis patients (n = 23), their close household contacts (n = 80), and community controls (n = 46) were tested at intervals over a period of up to two years. Latent infection or previous Mtb contact was assessed by ELISPOT and TST and complete blood counts were performed during the follow up. Results showed significant upregulation of FLIPs expression by infected individuals regardless of clinical status at entry to the study. A higher percentage of lymphocytes was found in the infected household contacts that remained healthy. In contrast, in individuals with active TB, a significant upregulation of TNFR2 expression, a significantly higher percentage of monocytes and a significantly decreased lymphocyte count were seen, compared to subjects that remained healthy. Moreover, the household contacts who subsequently developed signs of TB also had a significantly high number of monocytes. These data suggest tuberculosis may be associated with decreased T-cell survival (perhaps due to apoptosis) while inhibition of apoptosis in monocytes could lead to a relative increase in these cells: a situation predicted to favour Mtb. |
| Databáze: | OpenAIRE |
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