Class C CpG Oligodeoxynucleotide Immunomodulatory Response in Aged Squirrel Monkey (Saimiri Boliviensis Boliviensis)
One means of stimulating the mammalian innate immune system is via Toll-like receptor 9 (TLR9) being exposed to unmethylated cytosine-phosphate-guanine (CpG) DNA, also known as pathogen-associated molecular patterns (PAMPs) of microbial origin. Synthetic CpG oligodeoxynucleotides (ODNs) with defined...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2020.00036/full |
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| author | Pramod N. Nehete Pramod N. Nehete Lawrence E. Williams Sriram Chitta Bharti P. Nehete Akash G. Patel Margish D. Ramani Thomas Wisniewski Thomas Wisniewski Thomas Wisniewski Henrieta Scholtzova Henrieta Scholtzova |
| author_facet | Pramod N. Nehete Pramod N. Nehete Lawrence E. Williams Sriram Chitta Bharti P. Nehete Akash G. Patel Margish D. Ramani Thomas Wisniewski Thomas Wisniewski Thomas Wisniewski Henrieta Scholtzova Henrieta Scholtzova |
| author_sort | Pramod N. Nehete |
| collection | DOAJ |
| description | One means of stimulating the mammalian innate immune system is via Toll-like receptor 9 (TLR9) being exposed to unmethylated cytosine-phosphate-guanine (CpG) DNA, also known as pathogen-associated molecular patterns (PAMPs) of microbial origin. Synthetic CpG oligodeoxynucleotides (ODNs) with defined CpG motifs possess broad immunostimulatory properties that make CpG ODNs suitable as therapeutic interventions in a variety of human disease conditions, including Alzheimer’s disease (AD). Rodent models are often used to preclinically test the effectiveness of CpG ODN therapeutic agents for AD and other disorders. However, the translatability of findings in such models is limited due to the significant difference of the expression of TLR9 between primates and rodents. The squirrel monkey (SQM), a New World non-human primate (NHP), is known to be phylogenetically proximate to humans, and develops extensive age-dependent cerebral amyloid angiopathy (CAA), a key pathological feature of AD. Hence, this model is currently being used to test AD therapeutics. In the present study, we conducted the first examination of Class C CpG ODN’s immunomodulatory role in elderly SQMs. We documented the effectiveness of CpG ODN to trigger an immune response in an aged cohort whose immune system is senescent. The specific immune response patterns detected here closely resembled CpG ODN-induced immunostimulatory patterns observed in prior human studies. Overall, our findings provide critical data regarding the immunomodulatory potential of CpG ODN in this NHP model, allowing for future translational studies of innate immunity stimulation via TLR9 agonists for diverse indications, including AD therapeutics. |
| first_indexed | 2024-12-12T01:35:06Z |
| format | Article |
| id | doaj.art-2321ed39357b49d380c5a7a5f31be649 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-12T01:35:06Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-2321ed39357b49d380c5a7a5f31be6492022-12-22T00:42:51ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652020-03-011210.3389/fnagi.2020.00036517020Class C CpG Oligodeoxynucleotide Immunomodulatory Response in Aged Squirrel Monkey (Saimiri Boliviensis Boliviensis)Pramod N. Nehete0Pramod N. Nehete1Lawrence E. Williams2Sriram Chitta3Bharti P. Nehete4Akash G. Patel5Margish D. Ramani6Thomas Wisniewski7Thomas Wisniewski8Thomas Wisniewski9Henrieta Scholtzova10Henrieta Scholtzova11Department of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, United StatesThe University of Texas Graduate School of Biomedical Sciences, Houston, TX, United StatesDepartment of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, United StatesDepartment of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, United StatesDepartment of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, United StatesDepartment of Neurology, Center for Cognitive Neurology, New York University School of Medicine, New York, NY, United StatesDepartment of Pathology, New York University School of Medicine, New York, NY, United StatesDepartment of Neurology, Center for Cognitive Neurology, New York University School of Medicine, New York, NY, United StatesDepartment of Pathology, New York University School of Medicine, New York, NY, United StatesDepartment of Psychiatry, New York University School of Medicine, New York, NY, United StatesDepartment of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, United StatesDepartment of Neurology, Center for Cognitive Neurology, New York University School of Medicine, New York, NY, United StatesOne means of stimulating the mammalian innate immune system is via Toll-like receptor 9 (TLR9) being exposed to unmethylated cytosine-phosphate-guanine (CpG) DNA, also known as pathogen-associated molecular patterns (PAMPs) of microbial origin. Synthetic CpG oligodeoxynucleotides (ODNs) with defined CpG motifs possess broad immunostimulatory properties that make CpG ODNs suitable as therapeutic interventions in a variety of human disease conditions, including Alzheimer’s disease (AD). Rodent models are often used to preclinically test the effectiveness of CpG ODN therapeutic agents for AD and other disorders. However, the translatability of findings in such models is limited due to the significant difference of the expression of TLR9 between primates and rodents. The squirrel monkey (SQM), a New World non-human primate (NHP), is known to be phylogenetically proximate to humans, and develops extensive age-dependent cerebral amyloid angiopathy (CAA), a key pathological feature of AD. Hence, this model is currently being used to test AD therapeutics. In the present study, we conducted the first examination of Class C CpG ODN’s immunomodulatory role in elderly SQMs. We documented the effectiveness of CpG ODN to trigger an immune response in an aged cohort whose immune system is senescent. The specific immune response patterns detected here closely resembled CpG ODN-induced immunostimulatory patterns observed in prior human studies. Overall, our findings provide critical data regarding the immunomodulatory potential of CpG ODN in this NHP model, allowing for future translational studies of innate immunity stimulation via TLR9 agonists for diverse indications, including AD therapeutics.https://www.frontiersin.org/article/10.3389/fnagi.2020.00036/fullCpG ODN class Caged squirrel monkeycerebral amyloid angiopathycellular immune responseELISPOTcytokines |
| spellingShingle | Pramod N. Nehete Pramod N. Nehete Lawrence E. Williams Sriram Chitta Bharti P. Nehete Akash G. Patel Margish D. Ramani Thomas Wisniewski Thomas Wisniewski Thomas Wisniewski Henrieta Scholtzova Henrieta Scholtzova Class C CpG Oligodeoxynucleotide Immunomodulatory Response in Aged Squirrel Monkey (Saimiri Boliviensis Boliviensis) Frontiers in Aging Neuroscience CpG ODN class C aged squirrel monkey cerebral amyloid angiopathy cellular immune response ELISPOT cytokines |
| title | Class C CpG Oligodeoxynucleotide Immunomodulatory Response in Aged Squirrel Monkey (Saimiri Boliviensis Boliviensis) |
| title_full | Class C CpG Oligodeoxynucleotide Immunomodulatory Response in Aged Squirrel Monkey (Saimiri Boliviensis Boliviensis) |
| title_fullStr | Class C CpG Oligodeoxynucleotide Immunomodulatory Response in Aged Squirrel Monkey (Saimiri Boliviensis Boliviensis) |
| title_full_unstemmed | Class C CpG Oligodeoxynucleotide Immunomodulatory Response in Aged Squirrel Monkey (Saimiri Boliviensis Boliviensis) |
| title_short | Class C CpG Oligodeoxynucleotide Immunomodulatory Response in Aged Squirrel Monkey (Saimiri Boliviensis Boliviensis) |
| title_sort | class c cpg oligodeoxynucleotide immunomodulatory response in aged squirrel monkey saimiri boliviensis boliviensis |
| topic | CpG ODN class C aged squirrel monkey cerebral amyloid angiopathy cellular immune response ELISPOT cytokines |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2020.00036/full |
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