Enhancement of Dendritic Cell Antigen Cross-Presentation by CpG DNA Involves Type I IFN and Stabilization of Class I MHC mRNA
Abstract
Dendritic cells (DCs) internalize exogenous Ags and process them for cross-presentation by class I MHC (MHC-I) to CD8+ T cells. This processing can occur by transporter for Ag presentation (TAP)-dependent or TAP-independent mechanisms. We observed that CpG DNA enhanced cross-presentation of Ags by Flt-3L-cultured bone marrow-derived murine DCs by a type I IFN (IFN-αβ)-dependent mechanism. Myeloid DCs provided cross-presentation function in this system. Both TAP1 knockout and wild-type DCs showed enhanced cross-presentation when treated with CpG DNA at 26°C, demonstrating that TAP is not essential to this regulatory mechanism, although TAP is an important determinant of MHC-I expression. Enhancement of cross-processing by CpG DNA did not involve increased Ag uptake or proteolysis but did correlate with IFN-αβ-dependent increases in expression of MHC-I mRNA and protein. Increased MHC-I mRNA levels resulted in part from stabilization of MHC-I mRNA, a novel posttranscriptional mechanism for regulation of MHC-I expression. Thus, a major mechanism by which CpG oligodeoxynucleotide increase cross presentation by DCs appears to be an IFN-αβ-mediated increase in MHC-I synthesis.
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All of the AAV-induced cytokines and chemokines can be upregulated by activation of TLR9 in the periphery using synthetic CpG-rich oligonucleotides.
“all of the AAV-induced cytokines and chemokines can be upregulated by activation of TLR9 in the periphery using synthetic CpG-rich oligonucleotides.8,9,10,11,12,52,53,54,55,56,57,58”
From An innate immune response to adeno-associated virus genomes decreases cortical dendritic complexity and disrupts synaptic transmission (2024) · cites this paper as [53]
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- Authors
- Kuchtey, J., Chefalo, P. J., Gray, R. C., Ramachandra, L., & Harding, C. V.
- Affiliations
- Case Western Reserve University (US)
- ORCID
- Kuchtey, John
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-08
- Volume
- 175
- Issue
- 4
- Pages
- 2244-2251
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1631812628
- Cited by
- 66
- References
- 41
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2015: 1 · 2014: 4 · 2013: 3 · 2012: 2
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P-30 CA43703, P30CA043703)
- National Institute of Allergy and Infectious Diseases (R01AI034343, AI-34343, AI36219, AI47255, R01AI047255, AI055793, P30AI036219)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- dendritic cells, cross-presentation, CpG DNA, type I interferon, MHC class I, post-transcriptional regulation, TAP, myeloid dendritic cells, CD8+ T cells, Flt3L, bone marrow-derived dendritic cells
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily B, Member 2, Adjuvants, Immunologic, Animals, Cells, Cultured, Dendritic Cells, Half-Life, Mice, Inbred C57BL, Oligodeoxyribonucleotides, Ovalbumin, RNA, Messenger, Histocompatibility Antigens Class I, Signal Transduction, Up-Regulation, Interferon-alpha, Interferon-beta, Mice, Knockout, ATP-Binding Cassette Transporters, CpG Islands, RNA Stability, Cross-Priming, Mice
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