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P-glycoprotein (encoded by the <i>ABCB1</i> gene) has a dual role in regulating inflammation and reducing chemotherapy efficacy in various diseases, but there are few studies focused on pulmonary TB patients. In this study, our objective was to identify a list of genes that correlate with high and low levels of <i>ABCB1</i> gene expression in the lungs of pulmonary TB patients with different activity of chronic granulomatous inflammation. We compared gene expression in two groups of samples (with moderate and high activity of tuberculomas) to identify their characteristic gene signatures. Gene expression levels were determined using quantitative PCR in samples of perifocal area of granulomas, which were obtained from 65 patients after surgical intervention. Subsequently, two distinct gene signatures associated with high inflammation activity were identified. The first signature demonstrated increased expression of <i>HIF1a</i>, <i>TGM2</i>, <i>IL6</i>, <i>SOCS3</i>, and <i>STAT3</i>, which correlated with high <i>ABCB1</i> expression. The second signature was characterized by high expression of <i>TNFa</i> and <i>CD163</i> and low expression of <i>ABCB1</i>. These results provide insight into various inflammatory mechanisms and association with P-gp gene expression in lung tissue of pulmonary TB patients and will be useful in the development of a host-directed therapy approach to improving the effectiveness of anti-TB treatment.