The impact of Toll-like receptors on bacterial virulence strategies

Arpaia, Nicholas; Barton, Gregory M.

doi:10.1016/j.mib.2012.11.004

Cited by 20 publications

(19 citation statements)

References 70 publications

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“…This family comprises 13 members in mammals, ten in humans (TLR1-10) and 12 in mice (TLR1-9, TLR11-13) [67]. Most TLRs (TLR1, 2, 4, 5, 6 and 11) are localized on the cell surface, where they recognize mainly bacterial cell wall components (LPS of Gram negative bacteria by TLR4, lipoproteins from Grampositive bacteria by TLR1, 2 and 6, flagellin by TLR5), while some members in this family are localized intracellularly in the endosomes (TLR3, 7, 8 and 9) and recognize viral or bacterial nucleic acids [68,69].…”

Section: Immune Dysregulationmentioning

confidence: 99%

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gyires¹,

Tóth²,

Zádori

2014

CPD

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Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The two main forms of IBD are Crohn's disease and ulcerative colitis. According to the recent concept the disease is caused by a combination of factors, including genetics, immune dysregulation, barrier dysfunction and the change in microbial flora. Environmental factors, such as changes in diet, antibiotic use, smoking or improved domestic hygiene (e.g. eradication of intestinal helminths) probably contribute to the development and increased prevalence of IBD. Dysregulation of mucosal immunity in IBD causes an overproduction of inflammatory cytokines which resulted in uncontrolled intestinal inflammation. Based on extensive research over the last decade, besides the conventional therapy, there are several novel pathways and specific targets, on which focus new therapeutics. New therapeutics aim 1./ to correct genetic susceptibility by stimulating NOD2 expression, TLR3 signaling or inhibition of TLR4 pathway, 2./ to restore the immune dysregulation by inhibition of pro-inflammatory cytokines (TNF-, IL-6, IL-13, IL-17, IL-18, IL-21), Th1 polarisation (IL-2, IL-12, IL-23, IFN-), T-cell activation, leukocyte adhesion, as well as by immunostimulation (GM-CSF, G-CSF) and anti-inflammatory cytokines (IL-10, IL-11, IFN--1a), 3./ to restore mucosal barrier function and stimulate mucosal healing by different growth factors, such as GH, EGF, KGF, TGF-, VEGF, 4./ to restore the normal bacterial flora by antibiotics, probiotics. However, in spite of these numerous potential targets, the true value and clinical significance of most of the new biologics and molecules are not clear yet.

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Section: Immune Dysregulationmentioning

confidence: 99%

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gyires¹,

Tóth²,

Zádori

2014

CPD

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“…Expression and secretion of antimicrobial peptides (AMPs) such as βdefensins and cathelicidin can also be induced by TLRs upon detection of microbial ligands, which further supports the role of TLR-mediated detection in cell-intrinsic antimicrobial activity [60][61][62]. However, pathogens have evolved a variety of strategies to avoid TLR signaling such as altering their surface structures, interfering with TLR signaling pathways, and inhibiting, escaping, or subverting phagocytosis [52]. Brucella spp.…”

Section: General Aspects Of Toll-like Receptorsmentioning

confidence: 95%

“…TLR2 is activated by lipopeptides and other gram-positive bacterial components in conjunction with either TLR1 or TLR6; TLR4 detects LPS, which requires accessory protein MD-2; TLR5 detects flagellin; TLR3 detects poly I:C, a double-stranded RNA (dsRNA) analog; TLR9 detects unmethylated DNA and CpG-oligodeoxynucleotides (CpG-DNA) proposed to be delivered by Granulin and high mobility group (HMG) B proteins through an ability to bind simultaneously to both CpG-DNA and TLR9; and TLR7 is activated by single-stranded RNA and its synthetic analogs such as resiquimod, imiquimod, and loxoribine. All known TLR dimer structures display the same arrangement with the two carboxy-terminal tails closely juxtaposed and the amino termini at opposite ends but each varies in modes of ligand recognition [51][52][53][54]. This conformation may be required to bring the intracellular TIR domains into close proximity to initiate signaling.…”

Section: General Aspects Of Toll-like Receptorsmentioning

confidence: 99%

The Interaction Between Brucella and the Host Cell in Phagocytosis

Kim¹

2015

Updates on Brucellosis

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Brucella spp. are facultative intracellular parasitic pathogens that can survive and multiply in professional and nonprofessional phagocytes. These pathogens are responsible for brucellosis, which can cause abortion in domestic animals and undulant fever in humans. Brucella spp. can survive in a variety of cells and their virulence and chronic infections are thought to be due to their ability to evade the killing mechanisms within host cells, one of which is the inhibition of phagosomelysosome fusion. Lipid raft-associated molecules, such as GPI-anchored proteins, GM ganglioside, and cholesterol, are selectively integrated into Brucella-containing macropinosomes following the internalization of Brucella into macrophages, continuously sustaining a dynamic state of the phagosomal membrane. Toll-like receptors TLRs are important systems that detect microbial invasion via recognition of microbial components that triggers signaling pathways to promote the expression of genes and regulate innate immune responses. Recent several studies have revealed the importance between TLRs-Brucella interactions to control Brucella infection. Here, we reviewed selected aspects of lipid raft-associated molecules and TLRs-Brucella interaction, which may help to understand the mechanism of Brucella pathogenesis.

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“…(dsRNA) analog, is detected by TLR3; unmethylated DNA and CpG-oligodeoxynucleotides (CpG-DNA) are detected by TLR9, in which Granulin and high mobility group (HMG) B proteins have been proposed to deliver CpG-DNA to TLR9 through an ability to bind simultaneously to both CpG-DNA and TLR9; and single-stranded RNA and its synthetic analogs resiquimod, imiquimod, and loxoribine activate TLR7. Despite the variation in modes of ligand recognition, all known TLR dimer structures show the same arrangement, with the two carboxy-terminal tails closely juxtaposed and the amino termini at opposite ends of the dimer [2,9,10,44]. This conformation may be required in order to bring the intracellular TIR domains into close proximity for initiation of signaling.…”

Section: General Aspects Of Tlrs For Microbesmentioning

confidence: 99%

The key roles of toll-like receptor (TLR) for intracellular survival of Brucella

et al. 2013

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Brucella spp. are facultative intracellular pathogens that have the ability to survive and multiply in professional and nonprofessional phagocytes and cause abortion in domestic animals and undulant fever in humans. Brucella species can survive in a variety of cells, including macrophages and their virulence and chronic infections are thought to be due to their ability to avoid the killing mechanisms within macrophages. Inhibition of phagosome-lysosome fusion has been proposed as a mechanism for intracellular survival of Brucella in professional and nonprofessional phagocytes. Toll-like receptors (TLRs) are part of a skillful system for detection of invasion by microbial pathogens. Recognition of microbial components by TLRs triggers signaling pathways that promote expression of genes and regulate innate immune responses. Recent studies for the interaction between TLRs-Brucella have indicated the importance of control of Brucella infection. Here, we review selected aspects of TLRs-Brucella interaction, which may be helpful to understanding the mechanism of Brucella pathogenesis.

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The impact of Toll-like receptors on bacterial virulence strategies

Cited by 20 publications

References 70 publications

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

The Interaction Between Brucella and the Host Cell in Phagocytosis

The key roles of toll-like receptor (TLR) for intracellular survival of Brucella

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