Lipoproteins in <i>Staphylococcus aureus</i> Mediate Inflammation by TLR2 and Iron-Dependent Growth In Vivo

Schmaler, Mathias; Jann, Naja J.; Ferracin, Fabrizia; Landolt, Lea; Biswas, Lalitha; Götz, Friedrich; Landmann, Régine

doi:10.4049/jimmunol.0804292

Cited by 83 publications

(118 citation statements)

References 49 publications

(65 reference statements)

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…At later time points after infection (especially 24 h), tlr9 -/-mice had higher levels of IL-1β, IL-6, MIP-2 and KC in their BALF when compared with Wt mice, most likely, due to higher bacterial loads and activation of PRRs other than TLR9 by MRSA. Indeed, S. aureus can activate a variety of immune receptors, including TLR2 (34,35) and not establish to which extent cell-free DNA contributes to the host response during MRSA pneumonia. In addition, we cannot be certain which DNA source (host or pathogen) drives the immune response in our model.…”

Section: Tlr9 Deficiency Is Associated With Strongly Increased Lung Cmentioning

confidence: 99%

Toll-Like Receptor 9 Enhances Bacterial Clearance and Limits Lung Consolidation in Murine Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

Meer

Achouiti

Ende

et al. 2016

Mol Med

View full text Add to dashboard Cite

Section: Tlr9 Deficiency Is Associated With Strongly Increased Lung Cmentioning

confidence: 99%

Toll-Like Receptor 9 Enhances Bacterial Clearance and Limits Lung Consolidation in Murine Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

Meer

Achouiti

Ende

et al. 2016

Mol Med

View full text Add to dashboard Cite

“…In this study, we used Newman WT (25) and SA113 WT (ATCC 35558) strains and their isogenic lgt:ermB (Δlgt) mutants (10,26). Bacteria were grown in tryptic soy broth (TSB) for 7 h and subcultured overnight under the same conditions.…”

Section: Bacterial Strains and Growth Conditionsmentioning

confidence: 99%

“…TLR2 signals exclusively through MyD88, and cells lacking MyD88 produce no or low levels of cytokines after recognition of S. aureus (10,13,14). The failure of inflammatory defense appears responsible for the increased susceptibility of these mice to staphylococcal infections (10,(13)(14)(15)(16).…”

mentioning

confidence: 99%

“…Infections of cells and mice with S. aureus revealed that lipoproteins trigger the TLR2 signaling cascade, which is required for early activation of the innate immune system (9)(10)(11)(12). TLR2 signals exclusively through MyD88, and cells lacking MyD88 produce no or low levels of cytokines after recognition of S. aureus (10,13,14). The failure of inflammatory defense appears responsible for the increased susceptibility of these mice to staphylococcal infections (10,(13)(14)(15)(16).…”

mentioning

confidence: 99%

“…Several staphylococcal molecules are known to act as pathogenassociated molecular patterns for TLRs. Infections of cells and mice with S. aureus revealed that lipoproteins trigger the TLR2 signaling cascade, which is required for early activation of the innate immune system (9)(10)(11)(12). TLR2 signals exclusively through MyD88, and cells lacking MyD88 produce no or low levels of cytokines after recognition of S. aureus (10,13,14).…”

mentioning

confidence: 99%

See 2 more Smart Citations

T and B Cells Are Not Required for ClearingStaphylococcus aureusin Systemic Infection Despite a Strong TLR2–MyD88-Dependent T Cell Activation

Schmaler

Jann

Ferracin

et al. 2011

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Staphylococcus aureus infection elicits through its mature lipoproteins an innate immune response by TLR2–MyD88 signaling, which improves bacterial clearing and disease outcome. The role of dendritic cells (DCs) and T cells in this immune activation and the function of T and B cells in defense against S. aureus infection remain unclear. Therefore, we first evaluated DC and T cell activation after infection with S. aureus wild type (WT) and its isogenic mutant, which is deficient in lipoprotein maturation, in vitro. Lipoproteins in viable S. aureus contributed via TLR2–MyD88 to activation of DCs, which promoted the release of IFN-γ and IL-17 in CD4+ T cells. This strong effect was independent of superantigens and MHC class II. We next evaluated the function of T cells and their cytokines IFN-γ and IL-17 in infection in vivo. Six days after systemic murine infection IFN-γ, IL-17, and IL-10 production in total spleen cells were MyD88-dependent and their levels increased until day 21. The comparison of CD3−/−, Rag2−/−, and C57BL/6 mice after infection revealed that IFN-γ and IL-17 originated from T cells and IL-10 originated from innate immune cells. Furthermore, vaccination of mice to activate T and B cells did not improve eradication of S. aureus from organs. In conclusion, S. aureus enhances DC activation via TLR2–MyD88 and thereby promotes TH1 and TH17 cell differentiation. However, neither T cells and their MyD88-regulated products, IFN-γ and IL-17, nor B cells affected bacterial clearing from organs and disease outcome.

show abstract

Combating Implant Infections: Shifting Focus from Bacteria to Host

et al. 2020

View full text Add to dashboard Cite

commensal skin bacteria, Staphylococci, and in particular Staphylococcus aureus, have a strong tendency to colonize foreign bodies and cause IAI. [3,4] Important for the underlying pathophysiology, Staphylococci are highly competent at producing biofilms on implant surfaces, which encapsulate the bacterial niche from the outside environment, [5,6] thereby protecting the bacteria from host defense systems and antibiotics. [7] Antibiotics are administered as a routine procedure. [8] However, as a consequence of widespread antibiotics usage, bacteria are exposed to subinhibitory concentrations of antibiotics at a larger scale, driving their development toward antibiotic resistance, [9] as illustrated by the emergence of methicillin-resistant S. aureus (MRSA). [10,11] As an improvement over current clinically applied local antibiotics delivery systems, [12] the recent developments in implant surface engineering approaches allow better antimicrobial functionalities to be incorporated to allow for more tunable and controlled drug release. [13-15] The "race to the surface" model is popular among biomaterials researchers to predict the biomaterials fate, resulting from the competition between eukaryotic cells and bacteria at the material surface. [16] Using this template, implant antibacterial properties are being stemmed from direct contact killing mechanisms due to implant surface modifications [17,18] or firm immobilization of drugs, [19,20] as they both "shield" the implant from bacterial adhesion. The current anti-infective biomaterials strategies being explored can be categorized as: 1) implant functionalization with antibiotics or antibacterial drugs such as host defense peptides (HDPs), inorganic materials (e.g., chitosan and derivatives), and inorganics (e.g., silver, copper, and zinc metal nanoparticles (NPs)), 2) anti-biofilm surface modification (e.g., coating with antifouling polymers or quorum sensor inhibitors), or 3) physical surface changes for direct contact-killing properties (e.g., nanotubes, nanopillars, and metal implantation). [15,21] Emerging as a serious alternative or adjuvant therapy to antibiotics, bacteriophage (phage) therapy uses viruses responsible for the lysis of specific bacterial strains. [22,23] As a natural predator of bacteria, phages employ different killing mechanisms, making multidrug resistant bacteria susceptible for phages. [24] Moreover, phages are highly specific for pathogenic cells, which can eliminate disastrous off-target effects in the host. [25] As a limitation, the use of phage cocktails is needed for therapeutic efficacy, [26] while there is currently is no conclusive data on possible long-term side effects of phage therapy in The widespread use of biomaterials to support or replace body parts is increasingly threatened by the risk of implant-associated infections. In the quest for finding novel anti-infective biomaterials, there generally has been a one-sided focus on biomaterials with direct antibacterial properties, which leads to excessive use of antibacterial ag...

show abstract

Lipoproteins in Staphylococcus aureus Mediate Inflammation by TLR2 and Iron-Dependent Growth In Vivo

Cited by 83 publications

References 49 publications

Toll-Like Receptor 9 Enhances Bacterial Clearance and Limits Lung Consolidation in Murine Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

Toll-Like Receptor 9 Enhances Bacterial Clearance and Limits Lung Consolidation in Murine Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

T and B Cells Are Not Required for ClearingStaphylococcus aureusin Systemic Infection Despite a Strong TLR2–MyD88-Dependent T Cell Activation

Combating Implant Infections: Shifting Focus from Bacteria to Host

Contact Info

Product

Resources

About