Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell-penetrating peptide or combined with CpG

Download

index.pdf

Date

2015-04-01

Author

Yildiz, Soner
Alpdundar, Esin
Gungor, Bilgi
Kahraman, Tamer
Bayyurt, Banu
GÜRSEL, İHSAN
Gürsel, Mayda

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

208
views

0
downloads

Recognition of pathogen-derived nucleic acids by immune cells is critical for the activation of protective innate immune responses. Bacterial cyclic dinucleotides (CDNs) are small nucleic acids that are directly recognized by the cytosolic DNA sensor STING (stimulator of IFN genes), initiating a response characterized by proinflammatory cytokine and type I IFN production. Strategies to improve the immune stimulatory activities of CDNs can further their potential for clinical development. Here, we demonstrate that a simple complex of cylic-di-GMP with a cell-penetrating peptide enhances both cellular delivery and biological activity of the cyclic-di-GMP in murine splenocytes. Furthermore, our findings establish that activation of the TLR-dependent and TLR-independent DNA recognition pathways through combined use of CpG oligonucleotide (ODN) and CDN results in synergistic activity, augmenting cytokine production (IFN-/, IL-6, TNF-, IP-10), costimulatory molecule upregulation (MHC class II, CD86), and antigen-specific humoral and cellular immunity. Results presented herein indicate that 33-cGAMP, a recently identified bacterial CDN, is a superior stimulator of IFN genes ligand than cyclic-di-GMP in human PBMCs. Collectively, these findings suggest that the immune-stimulatory properties of CDNs can be augmented through peptide complexation or synergistic use with CpG oligonucleotide and may be of interest for the development of CDN-based immunotherapeutic agents.

Subject Keywords

Arginine peptide (nona-arginine), cGAMP, CpG ODN, Cyclic-di-GMP, Immunostimulation

URI

https://hdl.handle.net/11511/36772

Journal

EUROPEAN JOURNAL OF IMMUNOLOGY

DOI

https://doi.org/10.1002/eji.201445133

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

Regulation of Cytoskeletal Dynamics during T Cell Activation by Substrate Stiffness Özçelikkale, Altuğ; Upadhyaya, Arpita (2018-03-07) T lymphocytes are an integral part of the adaptive immune response. The detection of infectious agents critically depends on the interaction of T cells with antigen presenting cells, which have varying mechanical stiffness and complex topological features. It has been recently recognized that T cell activation is regulated both by stiffness of the antigen presenting surface and by cytoskeletal forces which partially arise from actomyosin contractility. However, the relationship between stiffness and ...
Differential immune activation following encapsulation of immunostimulatory CpG oligodeoxynucleotide in nanoliposomes. Erikçi, E; Gürsel, Mayda; Gürsel, I (2011-02-01) The immunogenicity of a vaccine formulation is closely related to the effective internalization by the innate immune cells that provide prolonged and simultaneous delivery of antigen and adjuvant to relevant antigen presenting cells. Endosome associated TLR9 recognizes microbial unmethylated CpG DNA. Clinical applications of TLR9 ligands are significantly hampered due to their pre-mature in vivo digestion and rapid clearance. Liposome encapsulation is a powerful tool to increase in vivo stability as well as...
Investigating the potential of bacillus calmette-guerin vaccine russia strain, cpg oligonucleotides and intravenous immunoglobulin to induce trained immunity in the context of antiviral immunity Baydemir, İlayda; Gürsel, Mayda; Department of Molecular Biology and Genetics (2020-10-12) Innate immune cells undergo metabolic and epigenetic reprogramming in response to specific stimuli, that enable a more robust immune response to secondary exposure to a wide variety of pathogens. This process of innate immune memory development has been termed as Trained Immunity (TI). BCG vaccine is one well-known inducer of innate immune memory. In vivo administration of CpG ODNs or Intravenous Immunoglobulin (IVIg) can also exert heterologous anti-microbial protective immunity. In this thesis, we sought ...
Structure-based design, synthesis and anticancer effect of cyclic Smac-polyarginine peptides Khalily, Melek Parlak; GEREKÇİ, Selin; Gulec, Ezgi A.; Özen, Can; Özçubukçu, Salih (2018-11-01) The second mitochondria-derived activator of caspase (Smac/DIABLO) is a pro-apoptotic protein that released from mitochondria into the cytosol when cells undergo apoptosis. Smac promotes caspase activation by binding the inhibitors of apoptosis proteins (IAP), particularly XIAP and eliminating their inhibitory activity. Although the seven N-terminal amino acids AVPIAQK (SmacN7) of Smac protein is able to elicit an anticancer response by itself, it is neither cell-permeable nor stable in the cellular environ...
Changes in expression profiles of antioxidant enzymes in diabetic rat kidneys SADİ, GÖKHAN; Eryilmaz, Nihan; Tutuncuoglu, Egemen; Cingir, Sahika; Güray, Nülüfer Tülün (2012-03-01) Background In diabetes mellitus, increased formation of reactive oxygen species due to high level of glucose in both blood plasma and tissues creates oxidative stress and damages the tissues. Antioxidants together with the antioxidant enzymes are very important in order to protect the cells against oxidative damage.

Citation Formats

S. Yildiz et al., “Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell-penetrating peptide or combined with CpG,” EUROPEAN JOURNAL OF IMMUNOLOGY, pp. 1170–1179, 2015, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/36772.