Toll-like receptor agonist lipopeptides self-assemble into distinct nanostructures

Hamley, Ian W.; Kirkham, Steven; Dehsorkhi, Ashkan; Castelletto, Valeria; Reza, Mehedi; Ruokolainen, Janne

doi:10.1039/c4cc07511k

Cited by 47 publications

(72 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Briefly, cells (1 ϫ 10 6 cells/experimental condition; 2 ϫ 10 6 cells/ml) were stimulated with anti-CD3 (clone OKT3; 5 g/ml) and anti-CD28 (clone 9.3; 2 g/ml) MAbs in the absence or presence of prewarmed (40°C) TLR2 agonist Pam3CSK4 (10 g/ml) for 30 min at 37°C under a 5% CO 2 atmosphere. The TLR2 ligand was subjected to a heat treatment to reduce its natural ability to adopt a self-assembled nanostructure (91). Cells next were fixed in 1 ml of 2% paraformaldehyde for 20 min at 4°C before being stained with PE-Cy7-conjugated anti-human CCR6 in 200 l of PBS-2 mM EDTA-0.5% BSA for 15 min at room temperature under dark conditions.…”

Section: Ethicsmentioning

confidence: 99%

Toll-Like Receptor 2 Ligation Enhances HIV-1 Replication in Activated CCR6 ⁺ CD4 ⁺ T Cells by Increasing Virus Entry and Establishing a More Permissive Environment to Infection

Bolduc

Ouellet

Hany

et al. 2017

J Virol

View full text Add to dashboard Cite

In this study, we investigated the effect of Toll-like receptor 2 (TLR2) ligation on the permissiveness of activated CD4 ϩ T cells to HIV-1 infection by focusing our experiments on the relative susceptibility of cell subsets based on their expression of CCR6. Purified primary human CD4 ϩ T cells were first subjected to a CD3/CD28 costimulation before treatment with the TLR2 agonist Pam3CSK4. Finally, cells were inoculated with R5-tropic HIV-1 particles that permit us to study the effect of TLR2 triggering on virus production at both population and single-cell levels. We report here that HIV-1 replication is augmented in CD3/CD28-costimulated CCR6 ϩ CD4 ϩ T cells upon engagement of the cell surface TLR2. Additional studies indicate that a higher virus entry and polymerization of the cortical actin are seen in this cell subset following TLR2 stimulation. A TLR2-mediated increase in the level of phosphorylated NF-B p65 subunit was also detected in CD3/CD28-costimulated CCR6 ϩ CD4 ϩ T cells. We propose that, upon antigenic presentation, an engagement of TLR2 acts specifically on CCR6 ϩ CD4 ϩ T cells by promoting virus entry in an intracellular milieu more favorable for productive HIV-1 infection.IMPORTANCE Following primary infection, HIV-1 induces an immunological and structural disruption of the gut mucosa, leading to bacterial translocation and release of microbial components in the bloodstream. These pathogen-derived constituents include several agonists of Toll-like receptors that may affect gut-homing CD4 ϩ T cells, such as those expressing the chemokine receptor CCR6, which are highly permissive to HIV-1 infection. We demonstrate that TLR2 ligation in CD3/ CD28-costimulated CCR6 ϩ CD4 ϩ T cells leads to enhanced virus production. Our results highlight the potential impact of bacterial translocation on the overall permissiveness of CCR6 ϩ CD4 ϩ T cells to productive HIV-1 infection. KEYWORDS CD4 ϩ T cells, NF-B, human immunodeficiency virus

show abstract

Section: Ethicsmentioning

confidence: 99%

Toll-Like Receptor 2 Ligation Enhances HIV-1 Replication in Activated CCR6 ⁺ CD4 ⁺ T Cells by Increasing Virus Entry and Establishing a More Permissive Environment to Infection

Bolduc

Ouellet

Hany

et al. 2017

J Virol

View full text Add to dashboard Cite

show abstract

“…This toxicity occurs independent of their sequences or lengths [59] in a manner that is similar to the aggregation of Aβ in Alzheimer's disease [60] or α-synuclein in Parkinson's disease [61]. Previous studies showed that Pam3-Cys, the synthetic N-terminus of ospA, self-assembled and showed aggregating potential in vitro assays [58,62], which can be related to brain tissue damage including the disruption of synaptic function.…”

Section: Advances In Lipoprotein Researchmentioning

confidence: 92%

Lipoproteins and Diseases of the Brain

Kim¹,

Palmore²

2017

Advances in Lipoprotein Research

View full text Add to dashboard Cite

Apolipoprotein E4 (apoE4) and outer surface protein A (ospA) are pathogenic lipoproteins involved in the progression of Alzheimer's disease and Lyme neuroborreliosis, respectively. Results from previous studies indicate that apoE4 exhibits neurotoxicity by activating amyloid beta pathways, and ospA causes damage to the brain by stimulating immune activity of microglia and astrocytes. These results, however, lack information about the specific interactions that develop between neurons and these two lipoproteins. It is essential to investigate the effect of these lipoproteins on neuronal morphology and function to better understand the mechanism of damage and disease of the brain. This chapter summarizes previous studies on the role of apoE4 and ospA in diseases of the brain and discusses experimental results from our own work that suggests new roles for apoE4 and ospA in neuronal outgrowth and synaptic loss.

show abstract

“…Lipopeptides, such as those incorporating the CSK 4 peptide motif and one, two or three palmitoyl (hexadecyl) chains [25], can also act as toll-like receptor (TLR) agonists, which have important applications in the treatment of disease. TLRs are transmembrane proteins that are very important in the immune system and as a result are therapeutic targets to treat disease.…”

Section: Toll-like Receptor Agonistsmentioning

confidence: 99%

Peptide hormones and lipopeptides: from self‐assembly to therapeutic applications

Hutchinson

Burholt

Hamley

2017

Journal of Peptide Science

View full text Add to dashboard Cite

This review describes the properties and activities of lipopeptides and peptide hormones and how the lipidation of peptide hormones could potentially produce therapeutic agents combating some of the most prevalent diseases and conditions. The self‐assembly of these types of molecules is outlined, and how this can impact on bioactivity. Peptide hormones specific to the uptake of food and produced in the gastrointestinal tract are discussed in detail. The advantages of lipidated peptide hormones over natural peptide hormones are summarised, in terms of stability and renal clearance, with potential application as therapeutic agents. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

show abstract

Toll-like receptor agonist lipopeptides self-assemble into distinct nanostructures

Cited by 47 publications

References 31 publications

Toll-Like Receptor 2 Ligation Enhances HIV-1 Replication in Activated CCR6 ⁺ CD4 ⁺ T Cells by Increasing Virus Entry and Establishing a More Permissive Environment to Infection

Toll-Like Receptor 2 Ligation Enhances HIV-1 Replication in Activated CCR6 ⁺ CD4 ⁺ T Cells by Increasing Virus Entry and Establishing a More Permissive Environment to Infection

Lipoproteins and Diseases of the Brain

Peptide hormones and lipopeptides: from self‐assembly to therapeutic applications

Contact Info

Product

Resources

About

Toll-like receptor agonist lipopeptides self-assemble into distinct nanostructures

Cited by 47 publications

References 31 publications

Toll-Like Receptor 2 Ligation Enhances HIV-1 Replication in Activated CCR6 + CD4 + T Cells by Increasing Virus Entry and Establishing a More Permissive Environment to Infection

Toll-Like Receptor 2 Ligation Enhances HIV-1 Replication in Activated CCR6 + CD4 + T Cells by Increasing Virus Entry and Establishing a More Permissive Environment to Infection

Lipoproteins and Diseases of the Brain

Peptide hormones and lipopeptides: from self‐assembly to therapeutic applications

Contact Info

Product

Resources

About

Toll-Like Receptor 2 Ligation Enhances HIV-1 Replication in Activated CCR6 ⁺ CD4 ⁺ T Cells by Increasing Virus Entry and Establishing a More Permissive Environment to Infection

Toll-Like Receptor 2 Ligation Enhances HIV-1 Replication in Activated CCR6 ⁺ CD4 ⁺ T Cells by Increasing Virus Entry and Establishing a More Permissive Environment to Infection