Resveratrol Inhibits the TRIF-Dependent Pathway by Upregulating Sterile Alpha and Armadillo Motif Protein, Contributing to Anti-Inflammatory Effects after Respiratory Syncytial Virus Infection

Abstract

Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in young children ELISA). SARM expression was reduced and TRIF expression was increased after infection with RSV. Resveratrol increased SARM expression and decreased TRIF expression after RSV infection. SARM knockdown in resveratrol-treated mice enhanced gamma interferon production, RSV-induced airway inflammation, and airway hyperresponsiveness (AHR). Resveratrol decreased TRIF expression and prevented the RSV-mediated reduction of SARM expression. Resveratrol-mediated inhibition of the TRIF-dependent pathway may be dependent on SARM expression. IMPORTANCEOur study provides insights into the regulation of innate immunity in response to RSV infection. The results suggest that resveratrol-mediated alterations in SARM have therapeutic potential against RSV immunopathology caused by deregulation of the TLR-mediated immune response. Ultimately, improved insight into the complex interplay between TLR adaptor proteins and the occurrence of severe RSV infection might lead to novel therapeutic treatment strategies, such as TLR adjuvants.

Resveratrol suppresses persistent airway inflammation and hyperresponsivess might partially via nerve growth factor in respiratory syncytial virus-infected mice

“…In our previous in vivo and in vitro studies, we found that resveratrol down-regulates the expression of TLR-TRIF to inhibit the production of RSV-induced IFN-γ and IL-6, which prevents RSV infection from causing acute airway inflammation and AHR [16][17][18]. Thus, in the present study, we investigated the effect of resveratrol on RSV-induced persistent airway inflammation and AHR and whether this effect was associated with IFN-γ.…”

“…Resveratrol reduced the release of steroid-resistant inflammatory cytokines (e.g., IL-6 and IL-8) to limit COPD [22]. Our previous studies [17,18,36] and others' reports [35,37] have shown that resveratrol can inhibit the TRIF signaling pathway to promote its anti-inflammatory effects, suggesting that resveratrol functions as an inhibitor of the TRIF signaling pathway. Interestingly, we also found that up-regulated TRIF can persist in lung tissue for at least 30 days following RSV infection.…”

“…The RSV-infected mice were treated as described previously [16,18,24]. The mice were infected intranasally with 3.4 × 10 5 PFU of RSV in a volume of 100 μl.…”

Beyond TLR Signaling—The Role of SARM in Antiviral Immune Defense, Apoptosis & Development

“…It is identified that SARM mediates neuronal cell death post-LACV infection [50]. Recently, it is described that Respiratory Syncytial Virus (RSV) infection resulted in decreased expression of mammalian SARM [55]. The decreased expression of SARM is correlated with increased inflammation post-RSV infection.…”

Role of dietary antioxidants in human metapneumovirus infection

“…In resveratrol treated cells, the amount of infectious viral particles reduced from almost a million/ml down to 50,000 and quercetin treatment reduced viral particles to little above 100,000. Resveratrol treatment has been shown to be protective against influenza (Palamara et al , 2005), RSV (Liu et al , 2014;Xie et al , 2012;Zang et al , 2011), herpes simplex virus 1 and 2 (Docherty et al , 1999;Faith et al , 2006), Epstein-Barr virus (De et al , 2011), human cytomegalovirus (Evers et al , 2004), varicella-zoster virus (Docherty et al , 2006) and polyomavirus (Berardi et al , 2009) infections, however it enhanced viral replication of Hepatitis C virus in vitro (Nakamura et al , 2010) and aggravated Theiler's murine encephalomyelitis virus-induced demyelinating disease in mice (Sato et al , 2013). Resveratrol treatment inhibition of influenza A virus replication was due to reduced expression of viral proteins through inhibition of a PKC-dependent pathway (Palamara et al , 2005).…”