TLR4 sensing of IsdB of <i>Staphylococcus aureus</i> induces a proinflammatory cytokine response via the NLRP3-caspase-1 inflammasome cascade

Abstract

The prevalence of multidrug-resistant <i>Staphylococcus aureus</i> is of global concern, and vaccines are urgently needed. The iron-regulated surface determinant protein B (IsdB) of <i>S. aureus</i> was investigated as a vaccine candidate because of its essential role in bacterial iron acquisition but failed in clinical trials despite strong immunogenicity. Here, we reveal an unexpected second function for IsdB in pathogen-host interaction: the bacterial fitness factor IsdB triggers a strong inflammatory response in innate immune cells via Toll-like receptor 4 and the inflammasome, thus acting as a novel pathogen-associated molecular pattern of <i>S. aureus</i>. Our discovery contributes to a better understanding of how <i>S. aureus</i> modulates the immune response, which is necessary for vaccine development against the sophisticated pathogen.