Toll-Like Receptors (TLRs) in Innate Immune Defense Against <i>Staphylococcus Aureus</i>

Pietrocola, Giampiero; Arciola, Carla Renata; Rindi, Simonetta; Poto, Antonella Di; Missineo, Antonino; Montanaro, Lucio; Speziale, Pietro

doi:10.5301/ijao.5000030

Cited by 70 publications

(61 citation statements)

References 96 publications

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“…Several studies have suggested that bacterial Lpps are pathogen-associated molecular patterns (PAMPs) sensed by the mammalian host through Toll-like receptor 2 (TLR2) heterodimerized with TLR1 or TLR6 to induce innate immunity activation and to control adaptive immunity (9 -12). TLR2 plays a critical role in the host response to the Gram-positive bacteria Staphylococcus aureus (13) and Streptococcus agalactiae (14). Although TLR2 has been considered a receptor for various structurally unrelated PAMPs, recent studies have suggested that, via their lipid moiety, bacterial Lpps function as the major, if not the sole, ligand molecules responsible for TLR2 activation (15).…”

mentioning

confidence: 99%

The Human Pathogen Streptococcus pyogenes Releases Lipoproteins as Lipoprotein-rich Membrane Vesicles

Biagini

Garibaldi

Aprea

et al. 2015

Molecular & Cellular Proteomics

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Bacterial lipoproteins are attractive vaccine candidates because they represent a major class of cell surfaceexposed proteins in many bacteria and are considered as potential pathogen-associated molecular patterns sensed by Toll-like receptors with built-in adjuvanticity. Although Gram-negative lipoproteins have been extensively characterized, little is known about Gram-positive lipoproteins. We isolated from Streptococcus pyogenes a large amount of lipoproteins organized in vesicles. These vesicles were obtained by weakening the bacterial cell wall with a sublethal concentration of penicillin. Lipid and proteomic analysis of the vesicles revealed that they were enriched in phosphatidylglycerol and almost exclusively composed of lipoproteins. In association with lipoproteins, a few hypothetical proteins, penicillin-binding proteins, and several members of the ExPortal, a membrane microdomain responsible for the maturation of secreted proteins, were identified. The typical lipidic moiety was apparently not necessary for lipoprotein insertion in the vesicle bilayer because they were also recovered from the isogenic diacylglyceryl transferase deletion mutant. The vesicles were not able to activate specific Toll-like receptor 2, indicating that lipoproteins organized in these vesicular structures do not act as pathogen-associated molecular patterns. In light of these findings, we propose to name these new structures Lipoprotein-rich Membrane Vesicles. Molecular & Cellular

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mentioning

confidence: 99%

The Human Pathogen Streptococcus pyogenes Releases Lipoproteins as Lipoprotein-rich Membrane Vesicles

Biagini

Garibaldi

Aprea

et al. 2015

Molecular & Cellular Proteomics

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“…Toll-like receptors (TLRs) are the most important class of innate PRRs by which host immune and non-immune cells are able to recognize pathogen-associated molecular patterns (PAMPs) (Pietrocola et al 2011). TLR2 plays a crucial role in recognizing PAMPs from a lot of pathogens including S. aureus.…”

Section: Discussionmentioning

confidence: 99%

The herbal-derived honokiol and magnolol enhances immune response to infection with methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA)

Choi

Kim

et al. 2015

Appl Microbiol Biotechnol

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The emergence of antibiotic resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) reminds us an urgent need to develop a new immune-modulating agent for preventing S. aureus infection. In this study, we found that herbal medicines, honokiol and magnolol, caused a significant cellular immune modulatory effect during S. aureus infection. In mouse macrophages, these compounds drove upregulation of an antioxidant effect in response to S. aureus, resulting in a dampened total cellular reactive oxygen species (ROS) production and decreased production of inflammatory cytokines/chemokines, whereas honokiol induced increased types I and III interferon messenger RNA (mRNA) expression levels in response to MSSA infection. Moreover, the internalization of S. aureus by human alveolar epithelial cells was inhibited by these compounds. Furthermore, honokiol and magnolol treatment promoted a delay in killing during MSSA infection in Caenorhabditis elegans, suggesting antimicrobial function in vivo. In conclusion, honokiol and magnolol may be considered as attractive immune-modulating treatment for S. aureus infection.

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“…Lipopolysaccharides (LPS) of Gram-negative bacteria are recognized by TLR-4, which is essential in inducing the Gram-negative inflammatory response [12]. Several danger molecules have been identified in Gram-positive bacteria, including various lipoproteins and lipoteichoic acid (LTA), and some of these danger molecules are recognized by TLR-2 [13][14][15]. CD14 is a promiscuous co-receptor for a number of TLRs and facilitates the signalling of both TLR-4 and TLR-2 [11,15].…”

Section: Introductionmentioning

confidence: 99%

The anti-inflammatory effect of combined complement and CD14 inhibition is preserved during escalating bacterial load

Egge

Barratt‐Due

Nymo

et al. 2015

Clinical and Experimental Immunology

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SummaryCombined inhibition of complement and CD14 is known to attenuate bacterial-induced inflammation, but the dependency of the bacterial load on this effect is unknown. Thus, we investigated whether the effect of such combined inhibition on Escherichia coli-and Staphylococcus aureus-induced inflammation was preserved during increasing bacterial concentrations. Human whole blood was preincubated with anti-CD14, eculizumab (C5-inhibitor) or compstatin (C3-inhibitor), or combinations thereof. Then heat-inactivated bacteria were added at final concentrations of 5 3 10 4 21 3 10 8 /ml (E. coli) or 5 3 10 7 24 3 10 8 /ml (S. aureus). Inflammatory markers were measured using enzyme-linked immunosorbent assay (ELISA), multiplex technology and flow cytometry. Combined inhibition of complement and CD14 significantly (P < 0.05) reduced E. coli-induced interleukin (IL)-6 by 40-92% at all bacterial concentrations. IL-1b, IL-8 and macrophage inflammatory protein (MIP)-1a were significantly (P < 0.05) inhibited by 53-100%, and the effect was lost only at the highest bacterial concentration. Tumour necrosis factor (TNF) and MIP-1b were significantly (P < 0.05) reduced by 80-97% at the lowest bacterial concentration. Monocyte and granulocyte CD11b were significantly (P < 0.05) reduced by 63-91% at all bacterial doses. Lactoferrin was significantly (P < 0.05) attenuated to the level of background activity at the lowest bacterial concentration. Similar effects were observed for S. aureus, but the attenuation was, in general, less pronounced. Compared to E. coli, much higher concentrations of S. aureus were required to induce the same cytokine responses. This study demonstrates generally preserved effects of combined complement and CD14 inhibition on Gram-negative and Grampositive bacterial-induced inflammation during escalating bacterial load. The implications of these findings for future therapy of sepsis are discussed.

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Toll-Like Receptors (TLRs) in Innate Immune Defense Against Staphylococcus Aureus

Cited by 70 publications

References 96 publications

The Human Pathogen Streptococcus pyogenes Releases Lipoproteins as Lipoprotein-rich Membrane Vesicles

The Human Pathogen Streptococcus pyogenes Releases Lipoproteins as Lipoprotein-rich Membrane Vesicles

The herbal-derived honokiol and magnolol enhances immune response to infection with methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA)

The anti-inflammatory effect of combined complement and CD14 inhibition is preserved during escalating bacterial load

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