TLR Signaling Is Required for Salmonella typhimurium Virulence

Arpaia, N. et al. Cell. 144, 675–688, 2011

Speaker: Chun-Hsien Fei (費俊憲)                       Time: 14:10~15:00, Mar, 28, 2012

Commentator: Prof. Lien-I Hor (何漣漪 老師)   Place: Room 601

Abstract

Toll-like receptors (TLRs) target a range of microbial ligands and activate innate immune responses  against microorganisms.  However, Salmonella typhimurium has developed several mechanisms to avoid host clearance.  S. typhimurium uses a type 3 secretion system encoded bySalmonella pathogenicity island 2 (SPI-2) to inject SPI-2 effectors into host cells to transform phagosomes into Salmonella-containing vacule (SCV) for replication.  The signals that are responsible for induction of SPI-2 genes still remain unclear.  The authors found that TLR 2, 4 and 9 knockout (TLR 2x4x9 KO) mice were less susceptible to S. typhimurium than TLR 2 and 4 knockout (TLR 2x4 KO) mice.  Immunoflourescent staining showed that the replication of S. typhimurium was limited in TLR 2x4x9 KO bone marrow-derived macrophages (BMMs).  Transmission EM data indicated that S. typhimurium could not for SCVs in TLR 2x4x9 KO BMMs.  They also found that S. typhimurium failed to induce SPI-2 genes expression and to secret SPI-2 effectors, which are necessary for intracellular growth, in TLR 2x4x9 KO BMMs.  Furthermore, they demonstrated that TLR-dependent phagosomal acidification is required for SPI-2 genes expression.  This study discovered that S. typhimurium uses TLR signaling to regulate virulence genes for contributing to a systemic infection.

References

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2.          Innate immunity cues virulence. Buckner, M. M. et al. Nature. 472, 179-180, 2011