Abstract
Toll-like receptors (TLRs) play an important role in mycobacterial infection, although little is known about the roles of these receptors, cytokines and nitric oxide during anti-tuberculosis treatment. Our objective was to evaluate the mRNA and cell surface expression of TLR2 and TLR4; inducible nitric oxide synthase (iNOS) expression; and cytokine Th1, Th2 and Th17 profiles in pulmonary tuberculosis patients at different time points of anti-tuberculosis treatment. Peripheral blood mononuclear cells (PBMCs) were obtained from PPD+ healthy controls and from patients receiving anti-tuberculosis treatment. Gene expression quantification was performed by qPCR, cell surface expression was assessed using flow cytometry, and cytokine quantification was conducted using the CBA technique. The treated patients presented higher gene expression and higher numbers of receptors on the cell surface of lymphocytes and monocytes than did control individuals. IL-12 and IFN-γ levels increased after the start of treatment, whereas TNF-α levels were reduced. TGF-β presented the highest levels during treatment. IL-10 and IL-17 expression and production tended to increase during treatment. iNOS gene expression was reduced throughout treatment in patients. Our results suggest that anti-tuberculosis treatment modulates the immune response, inducing an increase in the expression of TLRs and pro- and anti-inflammatory cytokines to combat bacteria and reduce the inflammatory process.
Highlights
Tuberculosis (TB) is an infectious disease with chronic evolution, and its etiological agent is the intracellular bacterium Mycobacterium tuberculosis (M. tuberculosis) [1]
TLR4 gene expression was significantly higher in pulmonary tuberculosis patients (TB) at the different time points of treatment (M1, p = 0.01; M2, p = 0.01; M3, p = 0.04) than in controls (C) (Figure 2B)
We evaluated the gene and cell surface expression of TLR2 and TLR4 in pulmonary tuberculosis patients during anti-tuberculosis treatment
Summary
Tuberculosis (TB) is an infectious disease with chronic evolution, and its etiological agent is the intracellular bacterium Mycobacterium tuberculosis (M. tuberculosis) [1]. Studies have shown that the recognition of mycobacterial products by TLRs leads to NF-kB activation and to gene transcription that produces pro-inflammatory cytokines, such as IL-12, TNF-a, IL-1b and nitric oxide [9]. Despite the protective effect of Th1 and Th17 responses against tuberculosis, the elevated expression of pro-inflammatory cytokines is related to disease immunopathogenesis [20,21]. To limit this deleterious action, anti-inflammatory mechanisms arise, represented by soluble TNF-a receptors that impede this cytokine’s binding to its receptor through signal blockade by regulatory T cells and the anti-inflammatory cytokines IL-4, IL-10 and TGF-b [21,22,23]
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