Fisetin Protects Against Listeria monocytogenes Infection by Reducing the Production of Listeriolysin O.

TO THE EDITOR—We read with great interest the recent publication by Wang et al about the direct interference of the flavonoid fisetin with the activity of the poreforming toxin listeriolysin O (LLO) from Listeria monocytogenes, which results in reduced virulence of the pathogen [1]. Recently, we found that pretreatment of the murine macrophages cell line P388D1 with fisetin prior to L. monocytogenes infection resulted in a reduction in L. monocytogenes-induced cell death (Figure 1A). This effect was dose dependent and was also observed for the lung epithelial cell line Beas-2B (data not shown). Furthermore, we also found a protective effect of fisetin pretreatment on macrophages (Figure 1A) and lung epithelial cells (data not shown) infected with Streptococcus pneumoniae. A major virulence factor of S. pneumoniae is pneumolysin (PLY), which, like LLO, is a member the cholesterol-dependent cytolysins. We extended these findings by examining the protective effect of fisetin on cells exposed to purified LLO and PLY [2, 3]. Surprisingly, fisetin pretreatment of macrophages and lung epithelial cells (data not shown) did not result in reduced hemolysin-induced cell death with either toxin. Preincubation of LLO with fisetin prior to addition to cells did not reduce cell death (Figure 1B). The hemolytic