The discovery of potent immunostimulatory CpG-ODNs widely distributed in bacterial genomes

Liu, Juan; Yan, Wei; Lu, Yue; Li, Yangyuling; Chen, Qian; Li, Yan

doi:10.1007/s12275-020-9289-y

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…The availability of TLR9 ligands in the endolysosome is tightly regulated by DNases (See Nucleases and the Sensing of Self versus Non-self DNA ). TLR9 preferentially detects ssDNA containing unmethylated cytosine-phosphate-guanine (CpG) motifs which are less frequent in eukaryotic self DNA (methylation of the C5 carbon of cytosine) compared to bacterial DNA( Coch et al., 2009 ; Hartmann and Krieg, 2000 ; Krieg et al., 1995 ), with a recent study identifying highly conserved stimulatory CpG-DNA fragments in multiple 16S and 23S rDNA sequences in bacterial genomes ( Liu et al., 2020 ). Moreover, a recent structural study reports that TLR9 has two binding sites, one binding ssDNA with an unmethylated CpG motif and the second binding short ssDNA carrying a 5′ hydroxyl ( Ohto et al., 2018 ).…”

Section: Main Textmentioning

confidence: 99%

Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids

2020

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All lifeforms have developed highly sophisticated systems equipped to detect altered self and non-self nucleic acids (NA). In vertebrates, NA-sensing receptors safeguard the integrity of the organism by detecting pathogens, dyshomeostasis and damage, and inducing appropriate responses to eliminate pathogens and reconstitute homeostasis. Effector mechanisms include i) immune signaling, ii) restriction of NA functions such as inhibition of mRNA translation, and iii) cell death pathways. An appropriate effector response is necessary for host defense, but dysregulated NA-sensing can lead to devastating autoimmune and autoinflammatory disease. Their inherent biochemical similarity renders the reliable distinction between self NA under homeostatic conditions and altered or exogenous NA particularly challenging. In this review, we provide an overview of recent progress in our understanding of the closely coordinated and regulated network of innate immune receptors, restriction factors, and nucleases to effectively respond to pathogens and maintain host integrity.

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Section: Main Textmentioning

confidence: 99%

Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids

2020

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“…During the last decade, CpG have been studied for their application in therapeutic and vaccine strategies, while are still limited the studies elucidating their stimulating role in the innate response to bacterial infections. These bacterial sequences are considered a type of Pathogen-Associated Molecular Pattern (PAMP) due to their abundance in bacterial genomes, and their immunostimulatory capacity against many intracellular pathogens, including Listeria monocytogenes, Leishmania major, Francisella tularensis, Klebsiella pneumonia [1][2][3][4][5][6] Staphylococcus aureus [7] and Mycobacterium tuberculosis (MTB) [8,[9][10][11] have been documented. Some studies were performed, primarily, to describe their adjuvant properties in mice, but few data are available on the eff ects of CpGs in humans.…”

Section: Introductionmentioning

confidence: 99%

A New CpG ODN Induces a Fine-Tuning of Innate Response Resulting in Mycobacterium tuberculosis Containment

Cappelli¹,

Giovannini²,

Basso³

et al. 2022

J Biomed Res Environ Sci

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Synthetic oligodeoxynucleotides containing bacterial CpG motifs trigger an immunomodulatory response that correlates with both the CpG hhhexamers and their flanking regions. In this study, four new phosphodiester backbone CpG ODNs were studied in the contest of the innate immune response to Mycobacterium tuberculosis (MTB) infection. Two out of the four CpG ODNs (CpG2 and CpG3) displayed significant and opposite immunomodulatory effects: CpG2 enhanced MTB containment by human Monocyte-Derived-Macrophages (MDM), while CpG3 promoted an increased pathogen growth, higher ROS and Labile Iron Pool (LIP) levels. Accordingly, for iron homeostasis genes transcription, CpG2 and CpG3 induced, respectively, an iron retention and iron release phenotype. Moreover, CpG2 induced NLRC4 and TRAF6 gene expression and repressed IKK alpha and TREM1 while CpG3 induced PPBP and IL-36 RN and repressed TRAF6, IL-1B, IL-1R2 and NF-kB2. After MTB infection, CpG2 increased the release of soluble TREM1 protein among many others as compared with fewer innate response-associated proteins induced by CpG3. We suggest that CpG2 helps the containment of MTB infection, by inducing an early tight balance of MDM activation players, including LIP, chemokines, ROS and TREM1 receptors. Oppositely, CpG3 induces in MDM an excessive and unregulated inflammatory response unable to contain MTB infection.

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Cell-free DNA beyond a biomarker for rejection: Biological trigger of tissue injury and potential therapeutics

Tsuji

Agbor‐Enoh

2021

The Journal of Heart and Lung Transplantation

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The discovery of potent immunostimulatory CpG-ODNs widely distributed in bacterial genomes

Cited by 3 publications

References 32 publications

Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids

Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids

A New CpG ODN Induces a Fine-Tuning of Innate Response Resulting in Mycobacterium tuberculosis Containment

Cell-free DNA beyond a biomarker for rejection: Biological trigger of tissue injury and potential therapeutics

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