Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran; Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran.
Cytokine. 2019 Mar;115:127-134. doi: 10.1016/j.cyto.2018.12.004. Epub 2018 Dec 26.
Macrophages are the primary phagocytes in the lungs and a part of the host defense system against Mycobacterium tuberculosis (Mtb), involved in the primary immune response. While several studies have assessed the effects of resistance to rifampin on Mtb physiology, the consequences of mutations in genes encoding the beta subunit of RNA polymerase (rpoB) for host-pathogen interactions remain poorly understood. In this study, rifampin-monoresistant (RMR) Mtb and H37Rv strains were used to infect the THP-1-derived macrophages. Real-time quantitative reverse transcription PCR assay was carried out to determine mRNA expression in 84 cytokine and chemokine genes. Production of specific cytokines and chemokines was measured by ELISA assay. In conclusion, the current study shed more light on the fitness cost of RMR strain and the potential effects of rpoB gene mutations on Mtb-host interactions. These results initially demonstrate that the Mtb carrying the rpoB-S450L can modulate macrophage responses to mediate bacterial survival.
巨噬细胞是肺部的主要吞噬细胞，也是宿主防御系统的一部分，可抵抗结核分枝杆菌（Mycobacterium tuberculosis，Mtb），参与初始免疫反应。虽然有几项研究评估了利福平耐药性对 Mtb 生理学的影响，但对于编码 RNA 聚合酶β亚基（rpoB）的基因突变对宿主-病原体相互作用的后果仍知之甚少。在这项研究中，使用利福平单耐药（Rifampicin-monoresistant，RMR）Mtb 和 H37Rv 菌株感染 THP-1 衍生的巨噬细胞。通过实时定量逆转录 PCR 测定法确定 84 种细胞因子和趋化因子基因的 mRNA 表达。通过 ELISA 测定法测量特定细胞因子和趋化因子的产生。总之，本研究进一步阐明了 RMR 株的适应度代价，以及 rpoB 基因突变对 Mtb-宿主相互作用的潜在影响。这些结果初步表明，携带 rpoB-S450L 的 Mtb 可以调节巨噬细胞反应，从而介导细菌存活。
