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Influenza A is one of the main infectious ailments threatening human wellness, and the seasonal influenza epidemic has been widely studied (Kanekiyo et al., 2013; Hutchinson, 2018). It was reported that the influenza A virus (IAV) infects around five of adults and 20 of young children worldwide each year, with as much as three million severe situations and 250,000 deaths (Zhou et al., 2014; Fontana and Steven, 2015). In line with the antigenicity of hemagglutinin (HA) and neuraminidase (NA) proteins, IAV is often categorized into many subtypes, like H1N1, H3N2, H5N1, H5N6, H7N9, and H9N2 (Park and Ryu, 2018). Preceding studies have shown thatCitation: Cui H, Zhang C, Zhang C, Cai Z, Chen L, Chen Z, Zhao K, Qiao S, Wang Y, Meng L, Dong S, Liu J and Guo Z (2022) AntiInfluenza Effect and Mechanisms of Lentinan in an ICR Mouse Model. Front. Cell. Infect. Microbiol. 12:892864. doi: ten.3389/fcimb.2022.Frontiers in Cellular and Infection Microbiology | frontiersin.orgMay 2022 | Volume 12 | ArticleCui et al.Anti-Influenza Effect of Lentinancross-species infection and transmission of avian influenza viruses including H5N1, H5N6, H7N9, and H9N2 confer a broad spectrum of disease with varying severity and mortality, posing a severe threat to public overall health and human overall health (To et al.Cathepsin B Protein Biological Activity , 2013; Zhang et al.IL-4 Protein Formulation , 2016; Um et al.PMID:23460641 , 2021). New strains of IAV with new pathogenicity and medication resistance evolve when HA and NA continue to mutate, resulting in seasonal influenza epidemics and localized outbreaks (Abdul-Careem et al., 2011; Perera and Peiris, 2015). Hence, there is an urgent need to develop additional successful novel anti-influenza drugs. IAV damages the physique by means of viral replication and an excessive inflammatory response (Lobo et al., 2019). Infection with IAV may also stimulate the body to generate excessive cytokine, although a cytokine storm may cause acute lung injury (ALI) in the host, which is the key cause of mortality (Fukuyama and Kawaoka, 2011). Toll-like receptors (TLRs) are an essential class of proteins involved in all-natural immunity and are also important receptors for the production of inflammatory mediators, amongst which TLR4 is closely related to pneumonia attributable to IAV (Martin and Wurfel, 2008). MyD88 is usually a linker protein that plays an particularly crucial role in TLR signaling (Li et al., 2009). MyD88 recruits IL-1R-associated kinases (IRAKs) that activate TRAF-6 through autophosphorylation. TRAF-6 activates nuclear aspect (NF)-kB, which induces related gene expression and secretes inflammatory cytokines (Downes and Marshall-Clarke, 2010). It has previously been shown that the activation of the TLR4 signaling pathway aggravates the lung damage caused by IAV (Imai et al., 2008; Nhu et al., 2010). Thus, inhibition in the cytokine storm and regulation from the TLR4 signaling pathway are specifically critical within the development of new anti-influenza drugs. Lentinan (LNT) is actually a b-1,3-glucan extracted from Lentinus edodes that has good biological activity and its security has also been affirmed (Mao et al., 2019; Kuang et al., 2021). LNT has immunomodulatory, anti-inflammatory, antiviral, and antitumor effects, and its very good anti-inflammatory and antiviral effects have already been extensively recognized worldwide in current years (Han et al., 2001; Ren et al., 2019; Chen et al., 2021; Yang et al., 2021; Du et al., 2022; Ya.