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Antiviral-Activated Dendritic Cells: A Paracrine-Induced Response State
Open accessAbstract
Infection of immature dendritic cells (DCs) by virus stimulates their maturation into APC. Infected DCs can also expose uninfected DCs to a panoply of cytokines/chemokines via paracrine signaling. Mathematical modeling suggests that a high rate of paracrine signaling is likely to occur among DCs located in three-dimensional space. Relatively little is known about how secreted factors modify the early response to virus infection. We used a transwell experimental system that allows passage of secreted factors, but not direct contact, between virus-infected DCs and uninfected DCs to investigate paracrine signaling responses. Paracrine signaling from infected DCs induced an antiviral-primed DC state distinct from that of mature virus-infected DCs that we refer to as antiviral-activated DCs (AVDCs). AVDCs had increased surface MHC class II and CD86 levels, but in contrast to virus-infected DCs, their MHC class I levels were unchanged. Imaging flow cytometry showed that AVDCs had an increased rate of phagocytosis compared with naive DCs. Experiments with IFN-β cytokine indicated that it may be responsible for CD86, but not MHC class II regulation in AVDCs. Both IFN-inducible and IFN-independent genes are up-regulated in AVDCs. Notably, AVDCs are relatively resistant to virus infection in comparison to naive DCs and achieve accelerated and augmented levels of costimulatory molecule expression with virus infection. AVDCs show a distinct antiviral-primed state of DC maturation mediated by DC paracrine signaling. Although further in vivo study is needed, the characteristics of the AVDC suggest that it is well suited to play a role in the early innate-adaptive transition of the immune system.
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A robust global normalization algorithm, using expression levels of the housekeeping genes ribosomal protein S11 (rps11), β-actin (actb), and α-tubulin (tuba), was used for all experiments.
“A robust global normalization algorithm, using expression levels of the housekeeping genes ribosomal protein S11 (rps11), -actin (actb), and ␣-tubulin (tuba), was used for all experiments, as described elsewhere (15,16).”
From Cytokine Response Is Determined by Duration of Receptor and Signal Transducers and Activators of Transcription 3 (STAT3) Activation (2013) · cites this paper as [15]
The Materials and Methods section (Quantitative RT PCR) names Rps11, Actb, and Tuba as housekeeping controls assayed in all samples and says mRNA measurements were normalized with a robust global normalization algorithm. It supports this procedure for the RNA measurements, but not the claim that the algorithm was used for all experiments, including experiments using other assays. (LLM, conf=0.85)
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Accuracy and calibration of commercial oligonucleotide and custom cDNA microarrays
Yuen, T. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.10.e48 · Cited by 520
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Braun, D. A., Fribourg, M., & Sealfon, S. C. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.386573 · Cited by 168
“Real-time PCR was performed using PlatinumTaqDNApolymerase (Invitrogen) and SYBRGreen (Invitrogen) on an ABI7900HT thermal cycler (Applied Biosystems), as described previously (15).”
MethodSelf-citation
Metadata
- Authors
- Bordería, A. V., Hartmann, B. M., Fernandez-Sesma, A., Moran, T. M., & Sealfon, S. C.
- Affiliations
- Department of Microbiology
- Department of Neurology
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-11
- Volume
- 181
- Issue
- 10
- Pages
- 6872-6881
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC4843808
- OpenAlex
- W2172274462
- Cited by
- 30
- References
- 1
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 3
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (HHSN 266200500021C)
- National Institute of Allergy and Infectious Diseases (HHSN272201000054C, U19 AI06231, HHSN266200500021C)
- 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 › interferon and immune responses
- Keywords
- dendritic cells, paracrine signaling, dendritic cell maturation, interferon-beta, MHC class II, CD86, phagocytosis, costimulatory molecules, viral infection, transwell assay, imaging flow cytometry
- MeSH terms
- Cells, Cultured, Dendritic Cells, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Phagocytosis, RNA Virus Infections, Signal Transduction, Gene Expression, Cytokines, Paracrine Communication, Reverse Transcriptase Polymerase Chain Reaction
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