Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll-like receptor 9 dependent T helper type 2 biased immune stimulation

Immunology
Jörg VollmerA M Krieg

Abstract

Oligodeoxynucleotides (ODN) with unmethylated CpG dinucleotides mimic the immune stimulatory activity of bacterial DNA in vertebrates and are recognized by Toll-like receptor 9 (TLR9). It is also possible to detect immune activation with certain phosphorothioate sequences that lack CpG motifs. These ODN are less potent than CpG ODN and the mechanism by which they stimulate mammalian leucocytes is not understood. We here provide several lines of evidence demonstrating that the effects induced by non-CpG ODN are mediated by TLR9. First, non-CpG ODN could not stimulate cytokine secretion from the splenocytes of TLR9-deficient (TLR9(-/-)) mice. Second, immunization of TLR9(+/+) but not TLR9(-/-) mice with non-CpG ODN enhanced antigen-specific antibody responses, although these were T helper type 2 (Th2)-biased. Third, reactivity to non-CpG ODN could be reconstituted by transfection of human TLR9 into non-responsive cells. In addition, we define a new efficient immune stimulatory motif aside from the CpG dinucleotide that consists of a 5'-TC dinucleotide in a thymidine-rich background. Non-CpG ODN containing this motif induced activation of human B cells, but lacked stimulation of Th1-like cytokines and chemokines. Our study indicat...Continue Reading

References

Apr 6, 1995·Nature·A M KriegD M Klinman
Sep 1, 1996·The Journal of Clinical Investigation·H LiangP E Lipsky
Jan 1, 1996·Antisense & Nucleic Acid Drug Development·A M KriegE Fisher
Dec 11, 1999·Biochemical Pharmacology·D S Pisetsky, C F Reich
Jan 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·G Hartmann, A M Krieg
Jan 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·G HartmannA M Krieg
May 12, 2000·Cellular Immunology·R B MannonD S Pisetsky
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·D P SesterK J Stacey
Dec 29, 2000·Nature·H HemmiS Akira
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·D VerthelyiD M Klinman
Jul 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·S BauerG B Lipford
Sep 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·F TakeshitaD M Klinman
Feb 28, 2002·Annual Review of Immunology·Arthur M Krieg
Aug 7, 2002·Antisense & Nucleic Acid Drug Development·Jorg VollmerArthur M Krieg
Feb 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kunio SanoGen Tamura
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fernanda EliasJuan M Rodriguez
Jan 13, 2004·Nature Immunology·Eicke LatzDouglas T Golenbock
Feb 19, 2004·European Journal of Immunology·Jörg VollmerArthur M Krieg
Feb 21, 2004·Science·Sandra S DieboldCaetano Reis e Sousa
Mar 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Koichi TabetaBruce Beutler

❮ Previous
Next ❯

Citations

Dec 7, 2010·European Journal of Nutrition·Mariko NakamotoTohru Sakai
Jun 10, 2006·Nature Reviews. Drug Discovery·Arthur M Krieg
Apr 24, 2009·Nucleic Acids Research·Stefan KippenbergerAugust Bernd
May 4, 2007·The Journal of Clinical Investigation·Arthur M Krieg
Jun 11, 2008·Journal of Immune Based Therapies and Vaccines·Curtis L CooperHeather L Davis
Aug 13, 2013·PloS One·Meltem Avci-AdaliHans P Wendel
Nov 21, 2007·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Marion Jurk, Jörg Vollmer
Jan 1, 2014·Fish & Shellfish Immunology·Omkar ByadgiTa-Chih Cheng
Jul 5, 2006·International Reviews of Immunology·Jörg Vollmer
Jun 7, 2005·Expert Opinion on Biological Therapy·Jörg Vollmer
May 19, 2009·Veterinary Immunology and Immunopathology·Eva Wattrang
Dec 17, 2008·Pulmonary Pharmacology & Therapeutics·Pinja IlmarinenHannu Kankaanranta
Dec 2, 2006·The Journal of Investigative Dermatology·Annette DornStefan Kippenberger
Sep 23, 2008·Immunology Letters·Cosima T Baldari
Aug 31, 2007·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Matthew P Bernard, Richard P Phipps
Jul 24, 2007·Vaccine·Valéria A ConfortiJerry J Reeves
Jul 28, 2015·Scientific Reports·Gandharva NagpalGajendra P S Raghava
Mar 15, 2005·Clinical and Experimental Immunology·P Lenert
Aug 5, 2005·International Journal of Cancer. Journal International Du Cancer·Ken J Ishii, Shizuo Akira
Mar 22, 2007·The Prostate·Joanna M IlvesaroKatri S Selander
Mar 25, 2006·Immunology·Petar LenertRobert F Ashman
Jan 31, 2009·European Journal of Immunology·Lei JiaoXi Yang
Aug 8, 2015·Journal of Cellular Physiology·Alessandra MiceraStefano Bonini
Sep 13, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·James L Watson, Derek M McKay

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.