Identification of Francisella tularensis Lipoproteins That Stimulate the Toll-like Receptor (TLR) 2/TLR1 Heterodimer

Thakur, Sonu Chand; Li, Hanfen; Lavine, Christy L.; Miller, Mark A.; Bina, James E.; Bina, Xiaowen R.; Re, Fabio

doi:10.1074/jbc.m706854200

Cited by 92 publications

(94 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…holarctica reacting with human tularemic sera. Interestingly, the glycosylated lipoproteins FTH_1071 and FTH_0414 were also previously found to interact with TLR-2/ TLR-1 heterodimers of HeLa cell lines, resulting in the induction of a proinflammatory response (512). Since interaction with these TLRs is generally mediated via acylation, glycosylation is thought to play a modulatory role, as shown by Sieling et al (513).…”

Section: Protein Glycosylationmentioning

confidence: 90%

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Tytgat

Lebeer

2014

Microbiol Mol Biol Rev

129

View full text Add to dashboard Cite

SUMMARY Humans have been increasingly recognized as being superorganisms, living in close contact with a microbiota on all their mucosal surfaces. However, most studies on the human microbiota have focused on gaining comprehensive insights into the composition of the microbiota under different health conditions (e.g., enterotypes), while there is also a need for detailed knowledge of the different molecules that mediate interactions with the host. Glycoconjugates are an interesting class of molecules for detailed studies, as they form a strain-specific barcode on the surface of bacteria, mediating specific interactions with the host. Strikingly, most glycoconjugates are synthesized by similar biosynthesis mechanisms. Bacteria can produce their major glycoconjugates by using a sequential or an en bloc mechanism, with both mechanistic options coexisting in many species for different macromolecules. In this review, these common themes are conceptualized and illustrated for all major classes of known bacterial glycoconjugates, with a special focus on the rather recently emergent field of glycosylated proteins. We describe the biosynthesis and importance of glycoconjugates in both pathogenic and beneficial bacteria and in both Gram-positive and -negative organisms. The focus lies on microorganisms important for human physiology. In addition, the potential for a better knowledge of bacterial glycoconjugates in the emerging field of glycoengineering and other perspectives is discussed.

show abstract

Section: Protein Glycosylationmentioning

confidence: 90%

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Tytgat

Lebeer

2014

Microbiol Mol Biol Rev

129

View full text Add to dashboard Cite

show abstract

“…TLR2 is the primary TLR involved in the inflammatory response to Francisella infection (1). Known Francisella TLR2 agonists include the uncharacterized lipoproteins LpnA/Tul4 and FTT_1103 (86,220). To our knowledge, TLR2 recognition of Francisella PGN has not been reported, and the status of PGN as a TLR2 ligand is still under debate (12,73,222).…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Subversion of Host Recognition and Defense Systems by Francisella spp

Jones

Napier

Sampson

et al. 2012

Microbiol Mol Biol Rev

125

151

View full text Add to dashboard Cite

SUMMARY Francisella tularensis is a Gram-negative intracellular pathogen and the causative agent of the disease tularemia. Inhalation of as few as 10 bacteria is sufficient to cause severe disease, making F. tularensis one of the most highly virulent bacterial pathogens. The initial stage of infection is characterized by the “silent” replication of bacteria in the absence of a significant inflammatory response. Francisella achieves this difficult task using several strategies: (i) strong integrity of the bacterial surface to resist host killing mechanisms and the release of inflammatory bacterial components (pathogen-associated molecular patterns [PAMPs]), (ii) modification of PAMPs to prevent activation of inflammatory pathways, and (iii) active modulation of the host response by escaping the phagosome and directly suppressing inflammatory pathways. We review the specific mechanisms by which Francisella achieves these goals to subvert host defenses and promote pathogenesis, highlighting as-yet-unanswered questions and important areas for future study.

show abstract

“…4C), we concluded that our recombinant proteins were not contaminated with TLR2 ligands. To further conclusively demonstrate that the proinflammatory effects of LukS and PVL depended on the proteins and not contaminating lipoproteins, we stimulated MH-S cells with LukS, PVL, and the lipoprotein Pam 3 CSK 4 in their native forms or after treatment with proteinase K or NaOH, which is known to hydrolyze the N-terminal acyl chains of bacterial lipoproteins (38). As shown in Supplemental Fig.…”

Section: Pvl Activates Transcription Of a Small Subset Of Nf-kb-regulmentioning

confidence: 99%

TLR 2 and CD14 Mediate Innate Immunity and Lung Inflammation to Staphylococcal Panton–Valentine Leukocidin In Vivo

Zivkovic

Sharif

Stich

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

The pore-forming toxin Panton–Valentine leukocidin (PVL) is carried by community-acquired methicillin-resistant Staphylococcus aureus and associated with necrotizing pneumonia together with poor prognosis of infected patients. Although the cell-death–inducing properties of PVL have previously been examined, the pulmonary immune response to PVL is largely unknown. Using an unbiased transcriptional profiling approach, we show that PVL induces only 29 genes in mouse alveolar macrophages, which are associated with TLR signaling. Further studies indicate that PVL directly binds to TLR2 and induces immune responses via NF-κB in a TLR2, CD14, MyD88, IL-1R–associated kinase 1, and TNFR-associated factor 6-dependent manner. PVL-mediated inflammation is independent of pore formation but strongly depends on the LukS subunit and is suppressed in CD14/TLR2−/− cells. In vivo PVL or LukS induced a robust inflammatory response in lungs, which was diminished in CD14/TLR2−/− mice. These results highlight the proinflammatory properties of PVL and identify CD14/TLR2 as an essential receptor complex for PVL-induced lung inflammation.

show abstract

Identification of Francisella tularensis Lipoproteins That Stimulate the Toll-like Receptor (TLR) 2/TLR1 Heterodimer

Cited by 92 publications

References 41 publications

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Subversion of Host Recognition and Defense Systems by Francisella spp

TLR 2 and CD14 Mediate Innate Immunity and Lung Inflammation to Staphylococcal Panton–Valentine Leukocidin In Vivo

Contact Info

Product

Resources

About