CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection.

Download

index.pdf

Date

2003-05-01

Author

Verthelyi, D
Gürsel, Mayda
Kenney, RT
Lifson, JD
Liu, S
Mican, J
Klinman, DM

Metadata

Show full item record

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

Item Usage Stats

221
views

0
downloads

Oligodeoxynucleotides containing CpG motifs (CpG ODNs) mimic microbial DNA and activate effectors of the innate immune response, which limits the spread of pathogens and promotes an adaptive immune response. CpG ODNs have been shown to protect mice from infection with intracellular pathogens. Unfortunately, CpG motifs that optimally stimulate humans are only weakly active in mice, mandating the use of nonhuman primates to monitor the activity and safety of "human" CpG ODNs in vivo. This study demonstrates that CpG ODN treatment of rhesus macaques significantly reduces the severity of the lesions caused by a challenge with Leishmania. Leishmania superinfection is common in immunocompromised hosts, particularly those infected with HIV. This study shows that PBMCs from HIV-infected subjects respond to stimulation with CpG ODNs. To determine whether CpG ODNs can protect retrovirus-infected primates, SIV-infected macaques were treated with CpG ODNs and then challenged with Leishmania. Both lesion size and parasite load were significantly reduced in the CpG-treated animals. These findings support the clinical development of CpG ODNs as immunoprotective agents in normal and HIV-infected patients.

Subject Keywords

Immunology

URI

https://hdl.handle.net/11511/40838

Journal

Journal of immunology (Baltimore, Md. : 1950)

DOI

https://doi.org/10.4049/jimmunol.170.9.4717

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

Cutting edge: Role of toll-like receptor 9 in CpG DNA-induced activation of human cells Takeshita, F; Leifer, CA; Gursel, I; Ishii, KJ; Takeshita, S; Gürsel, Mayda; Klinman, DM (The American Association of Immunologists, 2001-10-01) Unmethylated CpG motifs present in bacterial DNA stimulate a rapid and robust innate immune response. Human cell lines and PBMC that recognize CpG DNA express membrane-bound human Toll-like receptor 9 (hTLR9). Cells that are not responsive to CpG DNA become responsive when transfected with hTLR9. Expression of hTLR9 dramatically increases uptake of CpG (but not control) DNA into endocytic vesicles. Upon cell stimulation, hTLR9 and CpG DNA are found in the same endocytic vesicles. Cells expressing hTLR9 are ...
Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. Gursel, I; Gürsel, Mayda; Yamada, H; Ishii, KJ; Takeshita, F; Klinman, DM (The American Association of Immunologists, 2003-08-01) Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-te...
CpG RNA: identification of novel single-stranded RNA that stimulates human CD14+CD11c+ monocytes. Sugiyama, T; Gürsel, Mayda; Takeshita, F; Coban, C; Conover, J; Kaisho, T; Akira, S; Klinman, DM; Ishii, KJ (The American Association of Immunologists, 2005-02-15) Synthetic immunostimulatory nucleic acids such as CpG DNA are being harnessed therapeutically as vaccine adjuvants, anticancer or antiallergic agents. Efforts to identify nucleic acid-based agents capable of more specifically modulating the immune system are being developed. The current study identifies a novel class of single-stranded oligoribonucleotides (ORN) containing unmethylated CpG motifs and a poly(G) run at the 3 end (CpG ORN) that directly stimulate human CD14 CD11c monocytes but not dendritic ...
Suppressive oligodeoxynucleotides inhibit Th1 differentiation by blocking IFN-gamma- and IL-12-mediated signaling. Shirota, H; Gürsel, Mayda; Klinman, DM (The American Association of Immunologists, 2004-10-15) Repetitive TTAGGG motifs present at high frequency in mammalian telomeres can suppress Th1-mediated immune responses. Synthetic oligonucleotides (ODN) containing TTAGGG motifs mimic this activity and have proven effective in the prevention/ treatment of certain Th1-dependent autoimmune diseases. This work explores the mechanism by which suppressive ODN block the induction of Th1 immunity. Findings indicate that these ODN inhibit IFN- -induced STAT1 phosphorylation and IL-12- induced STAT3 and STAT4 phosphor...
Potential role of phosphatidylinositol 3 kinase, rather than DNA-dependent protein kinase, in CpG DNA-induced immune activation. Ishii, KJ; Takeshita, F; Gursel, I; Gürsel, Mayda; Conover, J; Nussenzweig, A; Klinman, DM (Rockefeller University Press, 2002-07-15) Unmethylated CpG motifs present in bacterial DNA stimulate a strong innate immune response. There is evidence that DNA-dependent protein kinase (DNA-PK) mediates CpG signaling. Specifically, wortmannin (an inhibitor of phosphatidylinositol 3 kinase [PI3]-kinases including DNA-PK) interferes with CpG-dependent cell activation, and DNA-PK knockout (KO) mice fail to respond to CpG stimulation. Current studies establish that wortmannin actually inhibits the uptake and colocalization of CpG DNA with toll-like re...

Citation Formats

D. Verthelyi et al., “CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection.,” Journal of immunology (Baltimore, Md. : 1950), pp. 4717–23, 2003, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/40838.