Phytoestrogens genistein and daidzein affect immunity in the nematode <i>Caenorhabditis elegans</i> via alterations of vitellogenin expression

<jats:sec><jats:title>Scope</jats:title><jats:p>Phytoestrogens, such as the soy isoflavones genistein and daidzein, are suggested to beneficially affect lipid metabolism in humans and thereby contribute to healthy ageing. New evidences show that phytoestrogens might slow ageing processes also by affecting immune processes.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>We tested in the nematode <jats:italic>Caenorhabditis elegans</jats:italic> the effects of 17β‐estradiol, genistein, and daidzein on resistance versus the nematode pathogen <jats:italic>Photorhabdus luminescens</jats:italic> with focus on vitellogenins, which are invertebrate estrogen‐responsive genes that encode homologues to ApoB100 with impact on immune functions. Here, we show that the estrogen 17β‐estradiol increases the resistance of <jats:italic><jats:styled-content style="fixed-case">C</jats:styled-content>. elegans</jats:italic> versus <jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content>. luminescens</jats:italic> by enhancing <jats:styled-content style="fixed-case">vitellogenin</jats:styled-content>‐expression at the m<jats:styled-content style="fixed-case">RNA</jats:styled-content> and protein level. Knockdown of single out of five functional vits by <jats:styled-content style="fixed-case">RNA</jats:styled-content>‐interference blunted the life‐extending effects under heat‐stress of 17β‐estradiol, demonstrating a lack of redundancy for the <jats:styled-content style="fixed-case">vitellogenin</jats:styled-content>s. <jats:styled-content style="fixed-case">RNA</jats:styled-content>i for nhr‐14, a suggested nuclear hormone receptor for estrogens, displayed no influence on 17β‐estradiol effects. The soy isoflavone genistein reduced <jats:styled-content style="fixed-case">vitellogenin</jats:styled-content>‐expression and also resistance versus <jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content>. luminescens</jats:italic> whereas daidzein increased resistance versus the pathogen in a <jats:styled-content style="fixed-case">vitellogenin</jats:styled-content>‐dependent manner.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our studies show that induction of estrogen‐responsive vitellogenin(s) by the phytoestrogen daidzein potently increases resistance of <jats:italic><jats:styled-content style="fixed-case">C</jats:styled-content>. elegans</jats:italic> versus pathogenic bacteria and heat whereas genistein acts in an antiestrogenic manner.</jats:p></jats:sec>