Cooperation of Oligodeoxynucleotides and Synthetic Molecules as Enhanced Immune Modulators
Identifieur interne : 000A19 ( Ncbi/Merge ); précédent : 000A18; suivant : 000A20Cooperation of Oligodeoxynucleotides and Synthetic Molecules as Enhanced Immune Modulators
Auteurs : Shireen Nigar [Bangladesh] ; Takeshi Shimosato [Japon]Source :
- Frontiers in Nutrition [ 2296-861X ] ; 2019.
Abstract
Unmethylated cytosine–guanine dinucleotide (CpG) motifs are potent stimulators of the host immune response. Cellular recognition of CpG motifs occurs via Toll-like receptor 9 (TLR9), which normally activates immune responses to pathogen-associated molecular patterns (PAMPs) indicative of infection. Oligodeoxynucleotides (ODNs) containing unmethylated CpGs mimic the immunostimulatory activity of viral/microbial DNA. Synthetic ODNs harboring CpG motifs resembling those identified in viral/microbial DNA trigger an identical response, such that these immunomodulatory ODNs have therapeutic potential. CpG DNA has been investigated as an agent for the management of malignancy, asthma, allergy, and contagious diseases, and as an adjuvant in immunotherapy. In this review, we discuss the potential synergy between synthetic ODNs and other synthetic molecules and their immunomodulatory effects. We also summarize the different synthetic molecules that function as immune modulators and outline the phenomenon of TLR-mediated immune responses. We previously reported a novel synthetic ODN that acts synergistically with other synthetic molecules (including CpG ODNs, the synthetic triacylated lipopeptide Pam3CSK4, lipopolysaccharide, and zymosan) that could serve as an immune therapy. Additionally, several clinical trials have evaluated the use of CpG ODNs with other immune factors such as granulocyte-macrophage colony-stimulating factor, cytokines, and both endosomal and cell-surface TLR ligands as adjuvants for the augmentation of vaccine activity. Furthermore, we discuss the structural recognition of ODNs by TLRs and the mechanism of functional modulation of TLRs in the context of the potential application of ODNs as wide-spectrum therapeutic agents.
Url:
DOI: 10.3389/fnut.2019.00140
PubMed: 31508424
PubMed Central: 6718720
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<front><div type="abstract" xml:lang="en"><p>Unmethylated cytosine–guanine dinucleotide (CpG) motifs are potent stimulators of the host immune response. Cellular recognition of CpG motifs occurs via Toll-like receptor 9 (TLR9), which normally activates immune responses to pathogen-associated molecular patterns (PAMPs) indicative of infection. Oligodeoxynucleotides (ODNs) containing unmethylated CpGs mimic the immunostimulatory activity of viral/microbial DNA. Synthetic ODNs harboring CpG motifs resembling those identified in viral/microbial DNA trigger an identical response, such that these immunomodulatory ODNs have therapeutic potential. CpG DNA has been investigated as an agent for the management of malignancy, asthma, allergy, and contagious diseases, and as an adjuvant in immunotherapy. In this review, we discuss the potential synergy between synthetic ODNs and other synthetic molecules and their immunomodulatory effects. We also summarize the different synthetic molecules that function as immune modulators and outline the phenomenon of TLR-mediated immune responses. We previously reported a novel synthetic ODN that acts synergistically with other synthetic molecules (including CpG ODNs, the synthetic triacylated lipopeptide Pam<sub>3</sub>
CSK<sub>4</sub>
, lipopolysaccharide, and zymosan) that could serve as an immune therapy. Additionally, several clinical trials have evaluated the use of CpG ODNs with other immune factors such as granulocyte-macrophage colony-stimulating factor, cytokines, and both endosomal and cell-surface TLR ligands as adjuvants for the augmentation of vaccine activity. Furthermore, we discuss the structural recognition of ODNs by TLRs and the mechanism of functional modulation of TLRs in the context of the potential application of ODNs as wide-spectrum therapeutic agents.</p>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Nutr</journal-id>
<journal-id journal-id-type="iso-abbrev">Front Nutr</journal-id>
<journal-id journal-id-type="publisher-id">Front. Nutr.</journal-id>
<journal-title-group><journal-title>Frontiers in Nutrition</journal-title>
</journal-title-group>
<issn pub-type="epub">2296-861X</issn>
<publisher><publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31508424</article-id>
<article-id pub-id-type="pmc">6718720</article-id>
<article-id pub-id-type="doi">10.3389/fnut.2019.00140</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Nutrition</subject>
<subj-group><subject>Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Cooperation of Oligodeoxynucleotides and Synthetic Molecules as Enhanced Immune Modulators</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Nigar</surname>
<given-names>Shireen</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/780867/overview"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Shimosato</surname>
<given-names>Takeshi</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="c001"><sup>*</sup>
</xref>
<xref ref-type="author-notes" rid="fn002"><sup>†</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/379217/overview"></uri>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup>
<institution>Department of Nutrition and Food Technology, Jashore University of Science and Technology</institution>
,<addr-line>Jashore</addr-line>
,<country>Bangladesh</country>
</aff>
<aff id="aff2"><sup>2</sup>
<institution>Department of Biomolecular Innovation, Institute for Biomedical Sciences, Shinshu University</institution>
,<addr-line>Nagano</addr-line>
,<country>Japan</country>
</aff>
<author-notes><fn fn-type="edited-by"><p>Edited by: Pinyi Lu, Biotechnology HPC Software Applications Institute (BHSAI), United States</p>
</fn>
<fn fn-type="edited-by"><p>Reviewed by: Margaret J. Lange, University of Missouri, United States; Bisheng Zhou, University of Illinois at Chicago, United States</p>
</fn>
<corresp id="c001">*Correspondence: Takeshi Shimosato <email>shimot@shinshu-u.ac.jp</email>
</corresp>
<fn fn-type="other" id="fn001"><p>This article was submitted to Nutritional Immunology, a section of the journal Frontiers in Nutrition</p>
</fn>
<fn fn-type="other" id="fn002"><p>†ORCID: Takeshi Shimosato <ext-link ext-link-type="uri" xlink:href="https://orcid.org/0000-0001-8132-1911">orcid.org/0000-0001-8132-1911</ext-link>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>27</day>
<month>8</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<volume>6</volume>
<elocation-id>140</elocation-id>
<history><date date-type="received"><day>17</day>
<month>5</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>13</day>
<month>8</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2019 Nigar and Shimosato.</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Nigar and Shimosato</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract><p>Unmethylated cytosine–guanine dinucleotide (CpG) motifs are potent stimulators of the host immune response. Cellular recognition of CpG motifs occurs via Toll-like receptor 9 (TLR9), which normally activates immune responses to pathogen-associated molecular patterns (PAMPs) indicative of infection. Oligodeoxynucleotides (ODNs) containing unmethylated CpGs mimic the immunostimulatory activity of viral/microbial DNA. Synthetic ODNs harboring CpG motifs resembling those identified in viral/microbial DNA trigger an identical response, such that these immunomodulatory ODNs have therapeutic potential. CpG DNA has been investigated as an agent for the management of malignancy, asthma, allergy, and contagious diseases, and as an adjuvant in immunotherapy. In this review, we discuss the potential synergy between synthetic ODNs and other synthetic molecules and their immunomodulatory effects. We also summarize the different synthetic molecules that function as immune modulators and outline the phenomenon of TLR-mediated immune responses. We previously reported a novel synthetic ODN that acts synergistically with other synthetic molecules (including CpG ODNs, the synthetic triacylated lipopeptide Pam<sub>3</sub>
CSK<sub>4</sub>
, lipopolysaccharide, and zymosan) that could serve as an immune therapy. Additionally, several clinical trials have evaluated the use of CpG ODNs with other immune factors such as granulocyte-macrophage colony-stimulating factor, cytokines, and both endosomal and cell-surface TLR ligands as adjuvants for the augmentation of vaccine activity. Furthermore, we discuss the structural recognition of ODNs by TLRs and the mechanism of functional modulation of TLRs in the context of the potential application of ODNs as wide-spectrum therapeutic agents.</p>
</abstract>
<kwd-group><kwd>ligands</kwd>
<kwd>molecule</kwd>
<kwd>ODN</kwd>
<kwd>synergy</kwd>
<kwd>TLR</kwd>
</kwd-group>
<funding-group><award-group><funding-source id="cn001">Japan Society for the Promotion of Science<named-content content-type="fundref-id">10.13039/501100001691</named-content>
</funding-source>
</award-group>
</funding-group>
<counts><fig-count count="1"></fig-count>
<table-count count="1"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="128"></ref-count>
<page-count count="11"></page-count>
<word-count count="8887"></word-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Bangladesh</li>
<li>Japon</li>
</country>
</list>
<tree><country name="Bangladesh"><noRegion><name sortKey="Nigar, Shireen" sort="Nigar, Shireen" uniqKey="Nigar S" first="Shireen" last="Nigar">Shireen Nigar</name>
</noRegion>
</country>
<country name="Japon"><noRegion><name sortKey="Shimosato, Takeshi" sort="Shimosato, Takeshi" uniqKey="Shimosato T" first="Takeshi" last="Shimosato">Takeshi Shimosato</name>
</noRegion>
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</tree>
</affiliations>
</record>
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