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

作者：Wen, Qian; Li, Yanfen; Han, Zhenyu; Liu, Honglin; Zhang, Shimeng; Chen, Yaoxin; He, Jianchun; Du, Xialin; Fu, Yuling; Zhang, Lijie; Zhang, Zelin; Huang, Yulan; Zhou, Xinying; Zhou, Chaoying; Hu, Shengfeng; Ma, Li^*

来源：Journal of Immunology, 2021, 206(11): 2623-2637.

DOI：10.4049/jimmunol.2001346

• INNATE IMMUNE-RESPONSES
• EXPRESSION
• BETA-ARRESTIN-2
• ACTIVATION
• PATHWAYS
• PROMOTES
• NECROSIS
• SCAFFOLD

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 beta-arrestin 2 mediates downstream signaling of G protein-coupled receptors. However, the role of beta-arrestin 2 in conferring immunity against M. tuberculosis has not yet been explored. We found that beta-arrestin 2 was upregulated in the lesioned regions of lung tissues in patients with tuberculosis. M. tuberculosis infection upregulated beta-arrestin 2 expression in human macrophages, and silencing of beta-arrestin 2 significantly enhanced bactericidal activity by enhancing the expression of proinflammatory cytokines such as TNF-alpha. beta-Arrestin 2 was shown to inhibit the activation of the TLR2/ERK1/2 pathway and its transcriptional regulation activity upon M. tuberculosis infection. Furthermore, beta-arrestin 2 transcriptionally regulates TNF-alpha by binding to CREB1. These observations revealed that the upregulation of beta-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 beta-arrestin 2 to modulate the TLR2-beta-arrestin 2-ERK1/2-CREB1-TNF-alpha regulatory axis.

• 单位
  南方医科大学