Peptidoglycan and Lipoteichoic Acid from<i>Staphylococcus aureus</i>Induce Tumor Necrosis Factor Alpha, Interleukin 6 (IL-6), and IL-10 Production in Both T Cells and Monocytes in a Human Whole Blood Model

Wang, J. E.; Jørgensen, Per; Almlöf, M.; Thiemermann, Christoph; Foster, Simon J.; Aasen, Ansgar O.; Solberg, Rigmor

doi:10.1128/iai.68.7.3965-3970.2000

Cited by 176 publications

(143 citation statements)

References 36 publications

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“…TLR2 expression on T cells has been observed (23), and both direct and indirect T cell costimulatory properties have been ascribed to TLR2 agonists (24,25). In addition, it has been shown in vitro that TLR2 agonists alone are able to activate T cells (26). Similar observations were reported for the TLR4 agonist LPS (27,28).…”

Section: Discussionsupporting

confidence: 59%

Introduction of Zwitterionic Motifs into Bacterial Polysaccharides Generates TLR2 Agonists Able to Activate APCs

Gallorini

Parente

Baronio

et al. 2007

The Journal of Immunology

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It was shown previously that bacterial polysaccharides (PS), which naturally contain both positive and negative charges, are able to activate T cells and APCs. However, the vast majority of bacterial PS are anionic and do not have these properties. In this study, we show that chemical introduction of positive charges into naturally anionic bacterial PS confers to the resulting zwitterionic PS (ZPS) the ability to activate pure human monocytes, monocyte-derived dendritic cells, and mouse bone marrow-derived dendritic cells, as do natural bacterial ZPS. Cells are induced to up-regulate MHC class II and costimulatory molecules and to produce cytokines. In mixed monocyte-T cell cocultures, ZPS induce MHC II-dependent T cell proliferation and up-regulation of activation markers. These stimulatory qualities of ZPS disappear when the positive charge is chemically removed from the molecules and thus the zwitterionic motif is destroyed. The ability of natural and chemically derived ZPS to activate APCs can be blocked by anti-TLR2 mAbs, and TLR2 transfectants show reporter gene transcription upon incubation with ZPS. In conclusion, the generation of a zwitterionic motif in bacterial PS confers the ability to activate both APCs and T cells. This finding has important implications for the design of novel polysaccharide vaccines.

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Section: Discussionsupporting

confidence: 59%

Introduction of Zwitterionic Motifs into Bacterial Polysaccharides Generates TLR2 Agonists Able to Activate APCs

Gallorini

Parente

Baronio

et al. 2007

The Journal of Immunology

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“…TNF-␣, INF-␥, IL-1␤, IL-6) and iNOS in myeloid cells that are key contributors to the sepsis syndrome. In keeping with these observations, studies using a human whole blood model indicated that lipoteichoic acid can induce expression of TNF-␣, IL-6, and IL-10 in a time-and dose-dependent manner (15). Collectively, these studies indicate that precise molecular mechanisms mediate the effects of Gram-positive bacterial endotoxins that contribute to the systemic inflammatory response syndrome.…”

mentioning

confidence: 51%

A Myeloid Hypoxia-inducible Factor 1α-Krüppel-like Factor 2 Pathway Regulates Gram-positive Endotoxin-mediated Sepsis

Mahabeleshwar

Qureshi

Takami

et al. 2012

Journal of Biological Chemistry

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Background: Gram-positive bacterial infections and sepsis are a significant cause of morbidity and mortality. Results: KLF2 inhibits Gram-positive, bacterial endotoxin-induced HIF-1␣ expression and macrophage activation. Conclusion: Transcription factors KLF2 and HIF-1␣ are critical regulator of Gram-positive sepsis. Significance: Pharmacological agents that modulate the KLF2/HIF-1 pathway may allow for therapeutic gain in the treatment of bacterial infections and sepsis.

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“…The most evident consequence of TLR stimulation is the induction of the inflammatory response. TLR ligation results in the production of pro-and anti-inflammatory cytokines (IL-1, IL-6, IL-8, IL-10, TNFα) [40][41][42], chemokines (IL-8, MCP-1) [43,44], defensins [45], and antiviral type-I interferons [46,47]. Other mechanisms attributed to TLR signaling are processes including apoptosis, tissue repair and angiogenesis.…”

Section: The Results Of Tlr Activation -Tlrs In Carcinogenesismentioning

confidence: 99%

Toll-like receptors and their role in carcinogenesis and anti-tumor treatment

Wolska

Lech‐Marańda

Robak

2009

Cellular and Molecular Biology Letters

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Toll-like receptors (TLRs) have been described as major components of the innate immune system, recognizing the conserved molecular structures found in the large groups of pathogens called pathogen-associated molecular patterns (PAMPs). TLR expression is ubiquitous, from epithelial to immunocompetent cells. TLR ligation triggers several adapter proteins and downstream kinases, leading to the induction of key pro-inflammatory mediators but also anti-inflammatory and anti-tumor cytokines. The result of this activation goes beyond innate immunity to shape the adaptive responses against pathogens and tumor cells, and maintains host homeostasis via cell debris utilization. TLRs have already become potent targets in infectious disease treatment and vaccine therapy and in neoplastic disease treatment, due to their ability to enhance antigen presentation. However, some studies show the dual effect of TLR stimulation on malignant cells: they can be proapoptotic or promote survival under different conditions. It is therefore crucial to design further studies assessing the biology of these receptors in normal and transformed cells. The established role of TLRs in human disease therapy is based on TLR7 and TLR4 agonists, respectively for the novel treatment of some types of skin cancer and for the anti-hepatitis B virus vaccine. Some clinical trials involving TLR agonists as potent enhancers of the anti-tumor response in solid tumors have begun.

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Peptidoglycan and Lipoteichoic Acid fromStaphylococcus aureusInduce Tumor Necrosis Factor Alpha, Interleukin 6 (IL-6), and IL-10 Production in Both T Cells and Monocytes in a Human Whole Blood Model

Cited by 176 publications

References 36 publications

Introduction of Zwitterionic Motifs into Bacterial Polysaccharides Generates TLR2 Agonists Able to Activate APCs

Introduction of Zwitterionic Motifs into Bacterial Polysaccharides Generates TLR2 Agonists Able to Activate APCs

A Myeloid Hypoxia-inducible Factor 1α-Krüppel-like Factor 2 Pathway Regulates Gram-positive Endotoxin-mediated Sepsis

Toll-like receptors and their role in carcinogenesis and anti-tumor treatment

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