Effects of Bacillus subtilis Natto Strains on Antiviral Responses in Resiquimod-Stimulated Human M1-Phenotype Macrophages

Bacillus subtilis natto is used in the production of natto, a traditional fermented soy food, and has beneficial immunomodulatory effects in humans. Single-stranded RNA (ssRNA) viruses, including influenza and coronavirus, often cause global pandemics. We proposed a human cell culture model mimicking ssRNA viral infection and investigated the ability of B. subtilis natto to induce antiviral effects in the model. The gene expressions were analyzed using quantitative real-time reverse transcription PCR. M1-phenotype macrophages derived from THP-1 cells strongly express the Toll-like receptor 8 (76.2-hold), CD80 (64.2-hold), and CCR7 (45.7-hold) mRNA compared to M0 macrophages. One µg/mL of resiquimod (RSQ)-stimulation induced the expression of IRF3 (1.9-hold), CXCL10 (14.5-hold), IFNβ1 (3.5-hold), ISG20 (4.4-hold), and MxA (1.7-hold) mRNA in the M1-phenotype macrophages. Based on these results, the RSQ-stimulated M1-phenotype macrophages were used as a cell culture model mimicking ssRNA viral infection. Moreover, the B. subtilis natto XF36 strain induced the expression of genes associated with antiviral activities (IFNβ1, IFNλ1, ISG20, and RNase L) and anti-inflammatory activities (IL-10) in the cell culture model. Thus, it is suggested that the XF36 suppresses viral infections and excessive inflammation by inducing the expression of genes involved in antiviral and anti-inflammatory activities.