Abstract
Cytokines play an essential role during active tuberculosis disease and cytokine genes have been described in association with altered cytokine levels. Therefore, the aim of this study was to verify if IFNG, IL12B, TNF, IL17A, IL10, and TGFB1 gene polymorphisms influence the immune response of Brazilian patients with pulmonary tuberculosis (PTB) at different time points of antituberculosis treatment (T1, T2, and T3). Our results showed the following associations: IFNG +874 T allele and IFNG +2109 A allele with higher IFN-γ levels; IL12B +1188 C allele with higher IL-12 levels; TNF −308 A allele with higher TNF-α plasma levels in controls and mRNA levels in PTB patients at T1; IL17A A allele at rs7747909 with higher IL-17 levels; IL10 −819 T allele with higher IL-10 levels; and TGFB1 +29 CC genotype higher TGF-β plasma levels in PTB patients at T2. The present study suggests that IFNG +874T/A, IFNG +2109A/G, IL12B +1188A/C, IL10 −819C/T, and TGFB1 +21C/T are associated with differential cytokine levels in pulmonary tuberculosis patients and may play a role in the initiation and maintenance of acquired cellular immunity to tuberculosis and in the outcome of the active disease while on antituberculosis treatment.
Highlights
Mycobacterium tuberculosis (M. tuberculosis) is an intracellular obligate aerobic pathogen which has a predilection for the lungs [1]
Results for the IFNG +2109A/G Single Nucleotide Polymorphism (SNP) showed that individuals with AA genotype presented higher levels of IFN-γ than the AG genotype in controls (P < 0.05) and in pulmonary tuberculosis (PTB) patients at T2 (P = 0.04) and T3 (P = 0.02) (Figure 2(a))
No significant differences in mRNA expression were seen between genotypes in the control group and in PTB patients, patients with the AA genotype tended to present with higher expression levels when compared to individuals with the AG genotype (Figure 2(b))
Summary
Mycobacterium tuberculosis (M. tuberculosis) is an intracellular obligate aerobic pathogen which has a predilection for the lungs [1]. Macrophages initiate phagocytosis of M. tuberculosis bacilli and regulate immune responses mediated by proinflammatory cytokines such as TNF-α. Effector T lymphocytes (T cells) and natural killer (NK) cells secrete IFNγ which activate alveolar macrophages to produce reactive intermediates from nitrogen and oxygen, inhibiting growth and promoting mycobacteria death [2]. IL-12, produced mainly by macrophages and dendritic cells, has a key role in the immune response to M. tuberculosis, bridging innate and adaptive immunity. IL-12 induces T cells and NK cells to produce proinflammatory cytokines such as IFNγ and TNF-α while regulating the production of IL-17 [2, 3]. A synergistic response of IFN-γ, IL-12, TNF-α and IL17 activates macrophage, stimulating these cells to eliminate
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