1. Academic Validation
  2. β-Arrestin 2 Regulates Inflammatory Responses against Mycobacterium tuberculosis Infection through ERK1/2 Signaling

β-Arrestin 2 Regulates Inflammatory Responses against Mycobacterium tuberculosis Infection through ERK1/2 Signaling

  • J Immunol. 2021 Jun 1;206(11):2623-2637. doi: 10.4049/jimmunol.2001346.
Qian Wen 1 Yanfen Li 1 Zhenyu Han 1 Honglin Liu 1 Shimeng Zhang 1 Yaoxin Chen 1 Jianchun He 1 Xialin Du 1 Yuling Fu 1 Lijie Zhang 1 Zelin Zhang 1 Yulan Huang 1 Xinying Zhou 1 Chaoying Zhou 1 Shengfeng Hu 1 Li Ma 2
Affiliations

Affiliations

  • 1 Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
  • 2 Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, People's Republic of China mali_61648322@smu.edu.cn.
Abstract

Mycobacterium tuberculosis, the pathogen that causes tuberculosis, exhibits complex host-pathogen interactions. Pattern Recognition Receptors and their downstream signaling pathways play crucial roles in determining the outcome of Infection. In particular, the scaffold protein β-arrestin 2 mediates downstream signaling of G protein-coupled receptors. However, the role of β-arrestin 2 in conferring immunity against M. tuberculosis has not yet been explored. We found that β-arrestin 2 was upregulated in the lesioned regions of lung tissues in patients with tuberculosis. M. tuberculosis Infection upregulated β-arrestin 2 expression in human macrophages, and silencing of β-arrestin 2 significantly enhanced bactericidal activity by enhancing the expression of proinflammatory cytokines such as TNF-α. β-Arrestin 2 was shown to inhibit the activation of the TLR2/ERK1/2 pathway and its transcriptional regulation activity upon M. tuberculosis Infection. Furthermore, β-arrestin 2 transcriptionally regulates TNF-α by binding to CREB1. These observations revealed that the upregulation of β-arrestin 2 is critical for M. tuberculosis to escape immune surveillance through an unknown mechanism. Our research offers a novel interference modality to enhance the immune response against tuberculosis by targeting β-arrestin 2 to modulate the TLR2-β-arrestin 2-ERK1/2-CREB1-TNF-α regulatory axis.

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