Anti-RSV Monoclonal antibody, Clone 4H9

Infections with respiratory syncytial virus (RSV) occurs repeatedly throughout life because sustained, protective memory responses fail to develop. Why this occurs is not known. During RSV infection the recognition of the virusviathe cytosolic RIG-I like receptors and signalingviathe adaptor protein MAVS is crucial for mounting an innate immune response. However, if this signaling pathway is important for T cell responses during primary infection and during re-infection is not fully elucidated. We describe a second peak of pro-inflammatory mediators during the primary immune response to RSV that coincides with the arrival of T cells into the lung. This second peak of cytokines/chemokines is regulated differently than the early peak and is largely independent of signalingviaMAVS. This was concurrent withMavs(-/-)mice mounting a strong T cell response to primary RSV infection, with robust IFN-gamma; and Granzyme B production. However, after RSV re-infection,Mavs(-/-)mice showed fewer CD4(+)and CD8(+)short term memory T cells and their capacity to produce IFN-gamma; and Granzyme B, was decreased. In sum, cytosolic recognition of RSV is important not only for initiating innate anti-viral responses but also for generating or maintaining efficient, short term T cell memory responses.

Exposure to benzo(a)pyrene (BaP) has been shown to cause mitochondrial dysfunction and injury to neural cells. Resveratrol (RSV) has been studied as an antioxidant, anti-inflammatory, anti-apoptotic, and anticancer agent and can modulate mitochondrial function in vitro and in vivo. However, the molecular mechanisms underlying RSV's protection against mitochondrial dysfunction have not been fully elucidated. To investigate whether RSV can effectively prevent BaP-induced mitochondrial dysfunction, we tested the effects of RSV in primary neuronal models. Our results confirmed that neurons exhibited mitochondrial dysfunction and apoptosis in the mitochondrial pathway after BaP-treatment, and that pretreatment with RSV could reduce that dysfunction. Further, our results indicated that RSV pretreatment enhanced mitochondrial biogenesis via the AMPK/PGC-1 alpha pathway and activated mitophagy via the PINK]-Parkin and AMPK/ULK1 pathways, thereby coordinating mitochondrial homeostasis. We also found that RSV could alleviate mitochondrial network fragmentation caused by BaP. This work provided insights into the role of RSV in preventing BaP-induced primary neuronal apoptosis in the mitochondrial pathway, mainly via regulation of mitochondrial biogenesis and mitophagy through AMPK pathway, thus maintaining the integrity of the mitochondrial network. (C) 2020 Elsevier Ltd. All rights reserved.