2. Academic Validation
  3. Activation of Nrf2 modulates protective immunity against Mycobacterium tuberculosis infection in THP1-derived macrophages

Activation of Nrf2 modulates protective immunity against Mycobacterium tuberculosis infection in THP1-derived macrophages

  • Free Radic Biol Med. 2022 Oct 14;193(Pt 1):177-189. doi: 10.1016/j.freeradbiomed.2022.10.274.
Jie Zhou 1,  Fang Fang 2,  Jinying Qi 2,  Tengteng Li 2,  Lin Zhang 2,  Hui Liu 2,  Jingzhu Lv 2,  Tao Xu 2,  Fengjiao Wu 2,  Chuanwang Song 2,  Wei Li 3,  Xiaojing Wang 3,  Xianyou Chang 4,  Hongtao Wang 2,  Ting Wang 5,  Zhongqing Qian 6
Affiliations

Affiliations

  • 1 Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui, 233030, China; Department of Clinical Laboratory, The Third People's Hospital of Bengbu, Bengbu Medical College, Bengbu, Anhui, 233000, China.
  • 2 Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui, 233030, China.
  • 3 Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Department of Respiration, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui, 233000, China.
  • 4 The Infectious Disease Hospital of Bengbu City, Bengbu, Anhui, 233000, China.
  • 5 Department of Internal Medicine, University of Arizona, Phoenix, AZ, 85004, USA. Electronic address: twang@email.arizona.edu.
  • 6 Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical College, Bengbu, Anhui, 233030, China. Electronic address: qzq7778@bbmc.edu.cn.
PMID: 36244589 DOI: 10.1016/j.freeradbiomed.2022.10.274
Abstract

Tuberculosis (TB), caused by mycobacterium tuberculosis (M. tuberculosis) Infection, is one of the leading causes of death globally and poses a threat to public health. During Infection, M. tuberculosis causes redox imbalance and dysfunctions of protective immunity. Transcription factor nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) is a major modulator of cellular redox homeostasis via transcriptional induction of cytoprotective genes to protect cell against the damage from insults. Thus, we hypothesize that Nrf2 may regulate protective immunity against M. tuberculosis. RNA-seq and immunoblotting results suggested that the expression of Nrf2 protein increased after M. tuberculosis Infection, and decreased upon long-term M. tuberculosis Infection, while Keap1 protein maintained a low expression level during M. tuberculosis Infection. Furthermore, Nrf2 activator sulforaphane (SFN) decreased proinflammatory cytokines production, phagocytosis and host cell Apoptosis, while increasing ROS levels and promoting Autophagy in THP1 macrophages infected with M. tuberculosis. In addition, SFN-activated Nrf2 augmented Bacterial killing by macrophages, which might be due to the regulation of protective immunity via Nrf2. Combined, our results extend the understanding of the complex innate immunity regulation by Nrf2 against mycobacterial Infection. Also, these findings suggested that the regulation of Nrf2 signaling cascade could be used as a therapeutic target for the treatment of TB patients and the development of better anti-TB vaccines.

Keywords

Macrophages; Mycobacterium tuberculosis; Nrf2; Protective immunity.

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