2. Academic Validation
  3. Melatonin suppresses TLR4-mediated RSV infection in the central nervous cells by inhibiting NLRP3 inflammasome formation and autophagy

Melatonin suppresses TLR4-mediated RSV infection in the central nervous cells by inhibiting NLRP3 inflammasome formation and autophagy

  • J Cell Mol Med. 2024 May;28(9):e18338. doi: 10.1111/jcmm.18338.
Yixuan Huang 1,  Chengcheng Jiang 2,  Xiaojie Liu 2,  Wei Tang 2,  Hongya Gui 2,  Tao Sun 2,  Doudou Xu 3,  Maozhang He 2,  Maozhen Han 4,  Huan Qiu 5,  Mingwei Chen 1,  Shenghai Huang 2 4 6
Affiliations

Affiliations

  • 1 Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 2 Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
  • 3 Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 4 School of Life Sciences, Anhui Medical University, Hefei, China.
  • 5 School of Nursing, Anhui Medical University, Hefei, China.
  • 6 Department of Clinical Laboratory, Anhui Public Health Clinical Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
PMID: 38683122 DOI: 10.1111/jcmm.18338
Abstract

Respiratory syncytial virus (RSV) infects neuronal cells in the central nervous system (CNS), resulting in neurological symptoms. In the present study, we intended to explore the mechanism of RSV infection-induced neuroinflammatory injury from the perspective of the immune response and sought to identify effective protective measures against the injury. The findings showed that Toll-like Receptor 4 (TLR4) was activated after RSV Infection in human neuronal SY5Y cells. Furthermore, TLR4 activation induced Autophagy and Apoptosis in neuronal cells, promoted the formation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and increased the secretion of downstream inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumour necrosis factor-α (TNF-α). Interestingly, blockade of TLR4 or treatment with exogenous melatonin significantly suppressed TLR4 activation as well as TLR4-mediated Apoptosis, Autophagy and immune responses. Therefore, we infer that melatonin may act on the TLR4 to ameliorate RSV-induced neuronal injury, which provides a new therapeutic target for RSV Infection.

Keywords

SH‐SY5Y cells; TLR4; autophagy; inflammasome; melatonin; respiratory syncytial virus.

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