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

The prevalence of multidrug-resistant is of global concern, and vaccines are urgently needed. The iron-regulated surface determinant protein B (IsdB) of was investigated as a vaccine candidate because of its essential role in bacterial iron acquisition but failed in clinical trials despite strong im...

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Bibliographic Details
Published in:mBio 2024-01, Vol.15 (1), p.e0022523-e0022523
Main Authors: Gonzalez, Juan José Izquierdo, Hossain, Md Faruq, Neef, Jolanda, Zwack, Erin E, Tsai, Chih-Ming, Raafat, Dina, Fechtner, Kevin, Herzog, Luise, Kohler, Thomas P, Schlüter, Rabea, Reder, Alexander, Holtfreter, Silva, Liu, George Y, Hammerschmidt, Sven, Völker, Uwe, Torres, Victor J, van Dijl, Jan Maarten, Lillig, Christopher H, Bröker, Barbara M, Darisipudi, Murty N
Format: Article
Language:English
Subjects:
Bacterial Proteins - immunology
Caspase 1 - metabolism
Cation Transport Proteins - immunology
cytokines
Cytokines - metabolism
Host-Microbial Interactions
Humans
Inflammasomes - metabolism
innate immunity
Iron - metabolism
IsdB
Methicillin-Resistant Staphylococcus aureus - immunology
NLR Family, Pyrin Domain-Containing 3 Protein - genetics
NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
NLRP3 inflammasome
Research Article
Staphylococcal Infections - immunology
Staphylococcus aureus
TLR4
Toll-Like Receptor 4 - metabolism
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Summary:The prevalence of multidrug-resistant is of global concern, and vaccines are urgently needed. The iron-regulated surface determinant protein B (IsdB) of 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 . Our discovery contributes to a better understanding of how modulates the immune response, which is necessary for vaccine development against the sophisticated pathogen.
ISSN:2150-7511
2150-7511
DOI:10.1128/mbio.00225-23