β-Glucan Derived from Aureobasidium pullulans Is Effective for the Prevention of Influenza in Mice

Abstract

β-(1→3)-D-glucans with β-(1→6)-glycosidic linked branches produced by mushrooms, yeast and fungi are known to be an immune activation agent, and are used in anti-cancer drugs or health-promoting foods. In this report, we demonstrate that oral administration of Aureobasidium pullulans -cultured fluid (AP-CF) enriched with the β-(1→3),(1→6)-D-glucan exhibits efficacy to protect mice infected with a lethal titer of the A/Puerto Rico/8/34 (PR8; H1N1) strain of influenza virus. The survival rate of the mice significantly increased by AP-CF administration after sublethal infection of PR8 virus. The virus titer in the mouse lung homogenates was significantly decreased by AP-CF administration. No significant difference in the mRNA expression of inflammatory cytokines, and in the population of lymphocytes was observed in the lungs of mice administered with AP-CF. Interestingly, expression level for the mRNA of virus sensors, RIG-I (retinoic acid-inducible gene-I) and MDA5 (melanoma differentiation-associated protein 5) strongly increased at 5 hours after the stimulation of A. pullulans -produced purified β-(1→3),(1→6)-D-glucan (AP-BG) in murine macrophage-derived RAW264.7 cells. Furthermore, the replication of PR8 virus was significantly repressed by pre-treatment of AP-BG. These findings suggest the increased expression of virus sensors is effective for the prevention of influenza by the inhibition of viral replication with the administration of AP-CF.

β-Glucan-supplemented diets increase poly(I:C)-induced gene expression of Mx, possibly via Tlr3-mediated recognition mechanism in common carp (Cyprinus carpio)

“…We have also shown that there is a differential expression profile where for example tlr3.1 was primarily up-regulated in the spleen, head kidney and mid gut whilst tlr3.2 was up-regulated in the head kidney and mid gut. We suggest that the up-regulation of tlr3 genes may explain why the injection of poly(I:C) specifically increased the expression levels of mx among other cytokines analysed, which is in concordance with reported increases of protection against viral pathogens conferred by β-glucan compounds in fish [9] and [10] and mammals [42]. Further assays on the expression levels of other virus sensing receptors in response to β-glucan and/or the functional groups from β-glucan with this activity are required to better understand the immunological activities of this immunostimulant and its role in virus defense.…”

“…RIG-I and MDA5, occurred 5 h after stimulation with β-glucan purified from Aureobasidium pullulans. Moreover, pre-treatment with this β-glucan compound conferred protection against the A/Puerto Rico/8/34 (PR8; H1N1) strain of influenza virus in vitro (RAW264.7 cells) and in vivo in orally administered mice [42]. Altogether, these results suggest an evolutionary conserved protective activity of β-glucans by means of increasing the sensitivity of treated cells to viral components.…”

“…tlr3.1 showed the highest levels of expression after feeding with β-glucans. Interestingly, in a recent publication [42] it has been shown that in murine macrophagederived RAW264.7 cells a significant increase in the transcript levels of other receptors involved in sensing viral components, i.e. RIG-I and MDA5, occurred 5 h after stimulation with β-glucan purified from Aureobasidium pullulans.…”

Yeasts in the Flowers of Wild Fleabane [Erigeron annus (L.) Pers.]

“…Isolates F-3 through F-99 and the remaining 25 isolates were not related to Group I. Generally, A. pullulans produces polysaccharides, including pullulan and β-glucan, which find industrial and medical applications (Yurlova and de Hoog, 1997;Cheng et al, 2011;Muramatsu et al, 2012). Recently, A. pullulans has been shown to produce (poly)malic acid (Nagata et al, 1993), lipase , laccase (Rich et al, 2011), mannitol oils (Price et al, 2013), biocontrol agents (Mari et al, 2012), biosurfactants , valuable lipids (Turk et al, 2004), and siderophores (Ma et al, 2012).…”

Regulation of Gene Expression by β-Glucans

“…Murine macrophageAureobasidium pullulans (Muramatsu et al, 2012) Ddx58 is RIG-1 (retinoic acid-IL-6, TNFα, GM-CSF derived RAW264.7 cells produced purified β (1->3), inducible gene-I). MDA5 is an and G-CSF…”