title: Decreased expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4⁺ T cells and peripheral blood from tuberculosis patients.
abstract: The vast majority of Mycobacterium tuberculosis (M. tuberculosis) infected individuals are protected from developing tuberculosis and T cells are centrally involved in this process. MicroRNAs (miRNA) regulate T-cell functions and are biomarker candidates of disease susceptibility and treatment efficacy in M. tuberculosis infection. We determined the expression profile of 29 selected miRNAs in CD4(+) T cells from tuberculosis patients and contacts with latent M. tuberculosis infection (LTBI). These analyses showed lower expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4(+) T cells from tuberculosis patients. Whole blood miRNA candidate analyses verified decreased expression of miR-26a, miR-29a, and miR-142-3p in children with tuberculosis as compared to healthy children with LTBI. Despite marked variances between individual donor samples, trends of increased miRNA candidate expression during treatment and recovery were observed. Functional in vitro analysis identified increased miR-21 and decreased miR-26a expression after re-stimulation of T cells. In vitro polarized Interleukin-17 positive T-cell clones showed activation-dependent miR-29a up-regulation. In order to characterize the role of miR-29a (a described suppressor of Interferon-γ in tuberculosis), we analyzed M. tuberculosis specific Interferon-γ expressing T cells in children with tuberculosis and healthy contacts but detected no correlation between miR-29a and Interferon-γ expression. Suppression of miR-29a in primary human T cells by antagomirs indicated no effect on Interferon-γ expression after in vitro activation. Finally, classification of miRNA targets revealed only a moderate overlap between the candidates. This may reflect differential roles of miR-21, miR-26a, miR-29a, and miR-142-3p in T-cell immunity against M. tuberculosis infection and disease.
authors.affiliation: Department of Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kleinsteuber
authors.forename: Kerrin
authors.initials: K
authors.lastname: Heesch
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schattling
authors.forename: Malte
authors.initials: M
authors.lastname: Kohns
authors.forename: Claudia
authors.initials: C
authors.lastname: Sander-Jülch
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.forename: Anneke
authors.initials: A
authors.lastname: Hesseling
authors.forename: Ertan
authors.initials: E
authors.lastname: Mayatepek
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleischer
authors.forename: Florian M
authors.initials: FM
authors.lastname: Marx
authors.forename: Marc
authors.initials: M
authors.lastname: Jacobsen
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D055985:Latent Tuberculosis / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D009841:Oligonucleotides / Q000494:pharmacology
chemical_list: D007371:Interferon-gamma; D020381:Interleukin-17; D035683:MicroRNAs; D009841:Oligonucleotides; C555159:MIRN142 microRNA, human; C524940:MIRN21 microRNA, human; C528163:MIRN26 microRNA, human; C532045:MIRN29a microRNA, human