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.ABSTRACTRespiratory 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.PMID:38683122 | PMC:PMC11057421 | DOI:10.1111/jcmm.18338
Source: Molecular Medicine - Category: Molecular Biology Authors: Source Type: research