DNA from Bacteria, but Not from Vertebrates, Induces Interferons, Activates Natural Killer Cells and Inhibits Tumor Growth

  title={DNA from Bacteria, but Not from Vertebrates, Induces Interferons, Activates Natural Killer Cells and Inhibits Tumor Growth},
  author={Saburo Yamamoto and Toshiko Yamamoto and Shizuo Shimada and Etsuro Kuramoto and Osamu Yano and Tetsuro Kataoka and Tohru Tokunaga},
  journal={Microbiology and Immunology},
The nucleic acid fraction from cells of 6 species of bacterium and 2 kinds of vertebrate, calf and salmon, was extracted and purified by the same procedures as described previously. When the spleen cells from BALB/c mice were incubated with the nucleic acid fraction from either of the bacteria, natural killer (NK) activity of the cells was remarkably elevated and the cells produced factors to activate macrophages and to inhibit viral growth. It was shown that the factor to activate macrophages… 
Activation of the innate immune system by CpG oligodeoxynucleotides: immunoprotective activity and safety
The precise sequence motifs in bacterial DNA responsible for this immune activation are defined, to establish the breadth and nature of such activation.
Historical Perspectives
The response of higher animals against immunostimulatory DNA must be the most primitive but important mechanism for self-nonself discrimination against foreign DNA.
IFN-gamma primes macrophage responses to bacterial DNA.
The results herein suggest the existence of a self-amplifying loop that may have implications for therapeutic applications of bacterial DNA.
Differences in Macrophage Activation by Bacterial DNA and CpG-Containing Oligonucleotides1
The structural differences between E. coli DNA and PO-ODN are assessed, which may explain the high activity of bacterial DNA on macrophages and the length dependence of the CpG ODN response was found to correlate with the presence in macrophage of a length-dependent uptake process for DNA.
Role of type I interferons in T cell activation induced by CpG DNA.
Reflecting the paucity of these motifs in vertebrate DNA — which is generally heavily methylated — purified DNA from humans, mice, frogs and fish are nonstimulatory for lymphoid cells, at least in terms of eliciting B-cell proliferation (Sun et al. 1997).
CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma.
Stimulatory CpG DNA motifs induced B, T, and natural killer cells to secrete cytokine more effectively than did lipopolysaccharide, suggesting immune recognition of bacterial DNA may contribute to the cytokine, as well as the antibody production characteristic of an innate inflammatory response.
Cutting edge: bacterial DNA and LPS act in synergy in inducing nitric oxide production in RAW 264.7 macrophages.
It is demonstrated that, although inducing little NO alone, DNA from both Gram-negative and Gram-positive bacteria synergizes with subthreshold concentrations of LPS to induce NO in cultures of RAW 264.7 macrophages.


In vivo augmentation of natural killer cell activity with a deoxyribonucleic acid fraction of BCG.
Antitumor activities of MY-1 were also abolished if the animals were pretreated with anti-asialo GM1 antiserum or carrageenan, suggesting that the activities can be ascribed mainly to activated NK cells.
Stimulation of in vitro murine lymphocyte proliferation by bacterial DNA.
These studies provide further evidence that DNA are not uniform in their immunologic activities likely because of their content of nonconserved structural determinants.
Synthetic Oligonucleotides with Particular Base Sequences from the cDNA Encoding Proteins of Mycobacterium bovis BCG Induce Interferons and Activate Natural Killer Cells
It is suggested that certain palindrome sequences, like GACGTC, GGCGCC and TGCGCA, are essential for 30‐mer oligonucleotides, like BCG‐A4a, to induce IFNs.
Induction of interferon synthesis by synthetic double-stranded polynucleotides
Whether a double-stranded deoxyribonucleic acid (DNA) polymer formed frompolydeoxyinosinic acid (dl) and polydeoxycytidylic acid (dC), as well as a double thestranded RNA-DNA homopolymer hybrid formed with rI and dC, could also induce interference and interferon synthesis in a cell culture is found.
Direct cytotoxicity of poly(dG, dC) at a concentration of 1,000 μg/ml against IMC cells was not observed in vitro, and the virus‐inhibitory activity of the supernatant was mostly neutralized by anti‐IFNα/β.
In vitro augmentation of natural killer activity of peripheral blood cells from cancer patients by a DNA fraction from Mycobacterium bovis BCG.
The NK activity in all of seven patients with gastric cancer, 12 patients with colonic cancer, and six patients with uterine cancer was augmented by incubation with Mycobacterium bovis BCG, although the degree of augmentation varied depending upon the origin of PBL.
Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity.
A fraction extracted from Mycobacterium bovis strain BCG, which was composed of 70% DNA, 28.0% RNA, 1.3% protein, 0.20% glucose, and 0.1% lipid, was found to possess strong antitumor activity, suggesting that the DNA from BCG possessed strong antitUMor activity under certain conditions.
The specificity of interferon induction in chick embryo cells by helical RNA.
  • C. Colby, M. Chamberlin
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1969
The high degree of specificity of the induction process is consistent with the existence of a specific intracellular receptor site, which may be a protein.
Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN [correction of INF] and augment IFN-mediated [correction of INF] natural killer activity.
The results strongly suggest that the presence of the unique palindromic sequences, such as GACGTC, AGCGCT, and AACGTT, but not ACCGGT, is essential for the immunostimulatory activity of oligonucleotides.
Inducers of interferon and host resistance. II. Multistranded synthetic polynucleotide complexes.
The discovery that certain multistranded polynucleotide complexes are highly active in microgram amounts in inducing interferon and host resistance in vivo arid in vitro is reported.