1. Academic Validation
  2. Activation of hypoxia-inducible factor 1 (Hif-1) enhanced bactericidal effects of macrophages to Mycobacterium tuberculosis

Activation of hypoxia-inducible factor 1 (Hif-1) enhanced bactericidal effects of macrophages to Mycobacterium tuberculosis

  • Tuberculosis (Edinb). 2021 Jan;126:102044. doi: 10.1016/j.tube.2020.102044.
Quan Li 1 Yuyu Xie 2 Zhangbo Cui 2 Hai Huang 1 Chengqing Yang 1 Baodong Yuan 1 Pei Shen 3 Chunwei Shi 4
Affiliations

Affiliations

  • 1 Wuhan Institute for Tuberculosis Control, Wuhan Pulmonary Hospital, Wuhan, 430030, PR China.
  • 2 Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
  • 3 Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China; School of Public Health, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai'an, 271016, PR China. Electronic address: shenpei1123@126.com.
  • 4 Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China. Electronic address: chunweishi@hust.edu.cn.
Abstract

Background: Tuberculosis is chronic Infection caused by Mycobacterium tuberculosis (M.tb), which infects specifically macrophages. Hif-1, hypoxia-inducible factor-1, was reported to act as master regulator of killing functions in macrophages.

Aim: To investigate whether Hif-1 activation would enhance bactericidal effect of macrophages and anti-tuberculosis effect of chemical reagent.

Methods: Hif-1 and LC3B were detected in tissues from pulmonary tuberculosis. U937, human monocytic leukemia cell line, was stimulated with PMA and differentiated into macrophages. Cells were pretreated with Hif-1 chemical inhibitor YC-1, stimulated with CoCl2 (Hif-1 activator), to detect LC3B with Western blot and confocal microscopy. Cells were infected with M. tb H37Rv strain, stimulated with CoCl2, following rifampine treatment. Expression of Autophagy markers was detected using Western blot. IL-6 and TNF-α were detected in cell supernatant with ELISA. Acid-fast staining and CFU assay were performed to evaluate intracellular Bacterial load.

Results and conclusions: Hif-1 and LC3B increased in tissues of pulmonary tuberculosis. Hif-1 activation enhanced Autophagy in M. tb infected U937 cells and production of IL-6 and TNF-α. Data from acid-fast staining and CFU indicated that Hif-1 activation enhanced anti-tuberculosis effect of rifampine in macrophages. Conclusively, to activate Hif-1 would strengthen bactericidal effect of macrophages, to further enhance anti-tuberculosis effect of chemical reagent.

Keywords

Autophagy; Hif-1; Macrophage; Mycobacterium tuberculosis; Rifampine.

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