Analysis of transcription factors, microRNAs and cytokines involved in T lymphocyte differentiation in patients with tuberculosis after directly observed treatment short-course.

Abstract

Tuberculosis (Tb) is an infectious disease in which the immune system plays an important role. MicroRNAs are involved in the development and maintenance of CD4 + T lymphocyte subpopulations. miR-326 regulates the differentiation to Th17 cells and miR-29 correlates with the Th1 response. The aim of this study was to determine the role of microRNAs, Transcription Factors, and cytokines in Th differentiation before and after the directly observed treatment short-course (DOTS). Peripheral blood mononuclear cells and serum from Tb patients were collected at times 0 (before therapy), 2 (after the intensive phase), and 6 months (after the holding phase). The cells were cultivated in presence or absence of ESAT-6 (10 μg/ml) and CFP-10 (10 μg/ml). Transcription Factor and microRNA expressions were analyzed by qPCR and cytokine production in both serum and culture supernatant using ELISA. A decrease in Th1 response with a diminishing in the relative expression of TBET and miR-29a at 2 and 6 months after the anti-Tb therapy (p < 0.01) were found. The miR-326 levels decreased after the intensive phase of the DOTS scheme. However, subdivision of the Tb patients according to gender, showed increased levels of miR-29a and miR-155 in females after the intensive phase of the therapeutic treatment when compared to time 0 and similar increased levels of miR-326 at time 6 versus time 0. In contrast, we observed a decrease in miR-326 levels in males at 6 months when compared to before therapy (time 0). In addition, high production of IL-17 in the culture supernatant was found at 2 and 6 months (p < 0.05) while in serum IL-17 was decreased. A positive correlation between IL-17 and RORC2 at time 6 was detected (p = 0.0202, r = 0.7880). In conclusion, these data suggest a reduction in Th1 and an induction of Th17 response after the anti-Tb therapy.

• Authors: Nancy Elizabeth Corral-Fernández, Juan Diego Cortes-García, Rivas-Santiago Bruno, Silvia Romano-Moreno, Susanna E Medellín-Garibay, Martín Magaña-Aquino, Raúl A Salazar-González, Roberto González-Amaro, Diana Patricia Portales-Pérez
• Journal: Tuberculosis (Edinburgh, Scotland) (Tuberculosis (Edinb)) Vol. 105 Pg. 1-8 (07 2017) ISSN: 1873-281X [Electronic] Scotland
• PMID: 28610780 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Antitubercular Agents
• Cytokines
• Interleukin-17
• MIRN155 microRNA, human
• MIRN29a microRNA, human
• MIRN326 microRNA, human
• MicroRNAs
• Nuclear Receptor Subfamily 1, Group F, Member 3
• RORC protein, human
• T-Box Domain Proteins
• T-box transcription factor TBX21
• Transcription Factors

Topics

• Adult
• Antitubercular Agents (therapeutic use)
• Cell Differentiation
• Cells, Cultured
• Cytokines (blood, genetics)
• Directly Observed Therapy
• Female
• Host-Pathogen Interactions
• Humans
• Interleukin-17 (blood)
• Male
• MicroRNAs (blood, genetics)
• Middle Aged
• Mycobacterium tuberculosis (drug effects, immunology)
• Nuclear Receptor Subfamily 1, Group F, Member 3 (blood)
• Prospective Studies
• T-Box Domain Proteins (blood)
• Th1 Cells (drug effects, immunology, metabolism, microbiology)
• Th17 Cells (drug effects, immunology, metabolism, microbiology)
• Time Factors
• Transcription Factors (blood, genetics)
• Treatment Outcome
• Tuberculosis (blood, drug therapy, immunology, microbiology)