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TLR4 sensing of IsdB of Staphylococcus aureus induces a proinflammatory cytokine response via the NLRP3-caspase-1 inflammasome cascade.

ABSTRACT:

Importance

The prevalence of multidrug-resistant Staphylococcus aureus is of global concern, and vaccines are urgently needed. The iron-regulated surface determinant protein B (IsdB) of S. aureus 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 S. aureus. Our discovery contributes to a better understanding of how S. aureus modulates the immune response, which is necessary for vaccine development against the sophisticated pathogen.

SUBMITTER: Gonzalez JJI

PROVIDER: S-EPMC10790753 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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

Gonzalez Juan José Izquierdo JJI Hossain Md Faruq MF Neef Jolanda J Zwack Erin E EE Tsai Chih-Ming C-M Raafat Dina D Fechtner Kevin K Herzog Luise L Kohler Thomas P TP Schlüter Rabea R Reder Alexander A Holtfreter Silva S Liu George Y GY Hammerschmidt Sven S Völker Uwe U Torres Victor J VJ van Dijl Jan Maarten JM Lillig Christopher H CH Bröker Barbara M BM Darisipudi Murty N MN

mBio 20231219 1

<h4>Importance</h4>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 tr ...[more]

PMID: 38112465

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