Gene Expression Study of Host and Mycobacterium tuberculosis Interactions in the Manifestation of Acute Tuberculosis.

Abstract

Mycobacterium tuberculosis (M.tb) could induce type IV hypersensitivity. The chemotaxis of the leukocytes toward the site of infection and producing matrix metalloproteinases (MMPs) are key factors in the immune pathogenesis of tuberculosis (TB). Mononuclear cells were isolated from bronchoalveolar lavage (BAL) specimens, and the target from genomic DNA was used for qPCR TB diagnosis and cDNA for specific RT-qPCR gene expression. The subjects were then classified into TB+ and TB- groups, and the expression levels of CFP-10, ESAT-6, CCR1, CCR12 and MMP3,9 were evaluated. The mean level of CCR1 expression in TB+ and TB- patients' BAL was 1.71 ± 0.78 and 0.5 ± 0.22, respectively, which was statistically different (p = 0.01). The CCR2 level, in TB+ (2.07 ± 1.4), was higher than in TB- patients (1.42 ± 0.89, p = 0.01). The MMP9 expression in TB+ was 2.56 ± 0.68, also higher than in TB- patients (1.13 ± 0.35), while MMP3 was lower in TB+ (0.22 ± 0.09) than in TB- (0.64 ± 0.230, p = 0.05). The CCR2/CCR1 and MMP3/MMP9 balance in TB+ were reduced, compared to the TB-. The CFP-10 and ESAT-6 were highly expressed in TB+ patients. The CFP-10 expression had a strong negative correlation with albumin (r = - 0.93, p = 0.001), and a negative correlation with neutrophil (r = - 0.444, p = 0.1 with 90% CI). The MMP-9 expression showed a positive correlation with WBC count (r = 0.61, p = 0.02), in TB+, and had a negative correlation with BMI (r = 0.59, p = 0.02) in TB-. The M.tb CFP-10 might be implicated in lowering CCR2 and MMP3 expression in favour of M.tb dissemination. Moreover, the balance of CCR2/CCR1 and MMP3/MMP9 can be used as prognostic factors in the severity of TB.