Airway administration of OM-85, a bacterial lysate, blocks experimental asthma by targeting dendritic cells and the epithelium/IL-33/ILC2 axis

The OM-85 bacterial lysate inhibits SARS-CoV-2 infection of epithelial cells by downregulating SARS-CoV-2 receptor expression

“…Especially notable was the upregulation of signature genes related to tight junctions and epithelial barrier function. 17 Interestingly, a preliminary analysis focused on the expression of the SARS-CoV-2 receptors Ace2 and Tmprss2 revealed a nominally significant (P 5 .02) inhibition of Ace2 expression in OM-85-treated mice compared with PBS-treated controls. Tmprss2 expression was also decreased, albeit not significantly (Fig 1 , B).…”

“…Our recent studies assessing how OM-85 administration to the airway compartment affects immune responses in the mouse lung 17 provided the first clue that OM-85 might affect SARS-CoV-2/host interactions. RNA-sequencing profiling of the lung transcriptome in Balb/c mice treated intranasally with OM-85 according to an optimized protocol (1 mg/treatment 3 14 treatments over 32 days, with terminal assessments at day 39: Fig 1, A) identified multiple genetic networks regulated by the lysate.…”

“…We chose the 7-day time point because it was optimal for inhibition of experimental allergic asthma and was used to generate the RNAsequencing data presented here. 17 However, the 2-day time point allowed us to explore shorter-term effects. Relative to PBS-treated mice, Tmprss2 was significantly downregulated at both time points (P 5 .01 and P 5 .003, respectively: Fig 1, D), whereas Ace2 was significantly (P 5 .01) inhibited only at the earlier time point (Fig 1, C).…”

“…Because OM-85 is a bacterial lysate whose ability to protect from asthma in vivo depends on Myd88/Trif innate immune signaling, 17 we then assessed whether OM-85-induced inhibition of Ace2 and Tmprss2 transcription in the mouse lung also required this pathway. These experiments, which were performed in C57BL/6 mice, revealed that as few as 4 intranasal treatments with OM-85 (1 mg/treatment: see Fig E1, A, in this article's Online Repository at www.jacionline.org) were sufficient to reduce Ace2 and Tmprss2 expression by 59% and 63%, respectively, in lung cells isolated from wild-type mice.…”

“…We recently found that OM-85 boosts human airway epithelial cell barrier function in vitro and regulates multiple airway barrier-related transcriptional networks in the lung following intranasal administration to mice. 17 These findings prompted us to investigate whether OM-85 also affects the expression of genes involved in SARS-CoV-2 infection of epithelial cells.…”