Effect of Water-Soluble Fraction from Lysozyme-TreatedEnterococcus faecalisFK-23 on Mortality Caused by Influenza A Virus in Mice

Abstract

To maintain homeostasis of the immune system is considered important for the prevention of influenza A virus infection. Aberrant systemic inflammation is frequently induced by influenza A virus infection, and the severity of the symptoms is associated with pathogenicity of the virus. Lactic acid bacteria are known to have a positive effect in maintaining the immune system. Furthermore, preparations of a lactic acid bacteria strain, Enterococcus faecalis FK-23 (FK-23), have been reported to exert preferable homeostatic effects on immune diseases such as allergic rhinitis and early asthmatic responses. In this study, we examined the efficacy of the water-soluble fraction of lysed and heat-treated FK-23 (SLFK) against a lethal influenza A virus challenge. Mice were orally administered SLFK from day -7 to day 20, and intranasally infected with influenza virus A/Puerto Rico/8/34 (H1N1) at 10(3) PFU on day 0. The survival rate of SLFK-administered mice after influenza A virus infection was significantly improved compared with that of control mice. In addition, the mRNA expression level of the anti-inflammatory cytokine interleukin-10 (IL-10) in lung tissues was enhanced by the oral administration of SLFK after influenza A virus infection. These observations suggest that the oral administration of SLFK exerts a protective effect against influenza virus infection through the activation of the anti-inflammatory response.

Enterococcus faecalis FK-23 affects alveolar-capillary permeability to attenuate leukocyte influx in lung after influenza virus infection

“…In this experiment, the LFK dose was fixed at 15 mg per mouse as previous report in which water-soluble fraction of LFK suspension (15 mg per mouse) was administered to mice ( Kondoh et al 2012 ). However, in this experiment, LFK suspension rather than water-soluble fraction of LFK was administered for comprehensive understanding of the mechanism for prevention of influenza by LFK.…”

“…We previously reported that oral administration of the soluble components of LFK, lysozyme-treated lactic acid bacteria E. faecalis FK-23, has an anti-influenza effect by upregulation of the anti-inflammatory cytokine IL-10 in lung ( Kondoh et al 2012 ). However, administration of the LFK suspension did not markedly upregulate IL-10 expression in this study (Figure 3A).…”

“…This discrepancy could be due to the differences in composition between administered samples. In this report, LFK suspension was administered to mice, while the supernatant of LFK suspension after centrifuge was used in the previous report ( Kondoh et al 2012 ). The present study demonstrated that LFK suspension has the ability to neither repress the viral replication, nor enhance the immune system in the lungs (Figures 1C, 3, and Additional file 3: Figure S3).…”

“…After washing with distilled water, the bacteria were treated with lysozyme, and then the reaction mixture was heated to 110°C for 10 min before lyophilization as described previously ( Kondoh et al 2012 ). LFK (15 mg/head, dissolved in 200 μl saline) or saline (200 μl) was orally administered using a feeding needle once a day.…”

“…These bacterial administrations help to enhance host’s immune response that causes the reduction of the viral replication efficiency and/or upregulation of cytokine expression. Previously, we reported that the water-soluble fraction of lysozyme-treated lactic acid bacterium Enterococcus faecalis FK-23 (LFK) reduces the mortality associated with influenza A virus infections ( Kondoh et al 2012 ). However, the mechanism underlying the anti-influenza effect of LFK remains unclear.…”