Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

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Inflammatory infiltration of the upper airway epithelium during Sendai virus infection: involvement of epithelial dendritic cells.

Journal of Virology ◽

10.1128/jvi.71.1.226-236.1997 ◽

1997 ◽

Vol 71 (1) ◽

pp. 226-236 ◽

Cited By ~ 66

Author(s):

A S McWilliam ◽

A M Marsh ◽

P G Holt

Keyword(s):

Dendritic Cells ◽

Virus Infection ◽

Airway Epithelium ◽

Sendai Virus ◽

Upper Airway ◽

Inflammatory Infiltration

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622. Effective Prevention of Spontaneous Lung Metastasis of AT6.3 Prostate Cancer by Intravenous Administration of Dendritic Cells Activated by Non-Transmissible Sendai Virus

Molecular Therapy ◽

10.1016/j.ymthe.2006.08.697 ◽

2006 ◽

Vol 13 ◽

pp. S240

Author(s):

Tomonori Kato ◽

Yasuji Ueda ◽

Yasuo Yoneyama ◽

Akinao Matsunaga ◽

Megumi Akizawa ◽

...

Keyword(s):

Prostate Cancer ◽

Dendritic Cells ◽

Lung Metastasis ◽

Intravenous Administration ◽

Sendai Virus ◽

Effective Prevention

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Provision of Continuous Maturation Signaling to Dendritic Cells by RIG-I–Stimulating Cytosolic RNA Synthesis of Sendai Virus

The Journal of Immunology ◽

10.4049/jimmunol.0901641 ◽

2010 ◽

Vol 186 (3) ◽

pp. 1828-1839 ◽

Cited By ~ 10

Author(s):

Shinji Okano ◽

Yoshikazu Yonemitsu ◽

Ken Shirabe ◽

Yoshihiro Kakeji ◽

Yoshihiko Maehara ◽

...

Keyword(s):

Dendritic Cells ◽

Rna Synthesis ◽

Sendai Virus

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Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells

Journal of Experimental Medicine ◽

10.1084/jem.20091627 ◽

2010 ◽

Vol 207 (4) ◽

pp. 823-836 ◽

Cited By ~ 480

Author(s):

Brian T. Edelson ◽

Wumesh KC ◽

Richard Juang ◽

Masako Kohyama ◽

Loralyn A. Benoit ◽

...

Keyword(s):

Dendritic Cells ◽

Transcription Factor ◽

Lymph Nodes ◽

Sendai Virus ◽

Pulmonary Inflammation ◽

Lymphoid Organ ◽

Contact Hypersensitivity ◽

Lymphoid Tissues ◽

Mesenteric Lymph Nodes ◽

Normal Contact

Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8α+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3−/− mice also lack CD103+CD11b− DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3−/− mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103+CD11b− DCs, with the population of CD103+CD11b+ DCs remaining intact. Batf3−/− mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103+ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8α+ cDCs and nonlymphoid CD103+ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ–resident CD8α+ cDCs and nonlymphoid CD103+ DCs.

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PP-093 Sustained highly efficient prevention of lung metastasis of murine prostate cancer induced by dendritic cells harboring recombinant Sendai virus(The 97th Annual Meeting of the Japanese Urological Association)

The Japanese Journal of Urology ◽

10.5980/jpnjurol.100.340_1 ◽

2009 ◽

Vol 100 (2) ◽

pp. 340

Keyword(s):

Prostate Cancer ◽

Dendritic Cells ◽

Annual Meeting ◽

Lung Metastasis ◽

Sendai Virus ◽

Highly Efficient

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Gene Expression and Antiviral Activity of Alpha/Beta Interferons and Interleukin-29 in Virus-Infected Human Myeloid Dendritic Cells

Journal of Virology ◽

10.1128/jvi.79.15.9608-9617.2005 ◽

2005 ◽

Vol 79 (15) ◽

pp. 9608-9617 ◽

Cited By ~ 134

Author(s):

Pamela Österlund ◽

Ville Veckman ◽

Jukka Sirén ◽

Kevin M. Klucher ◽

John Hiscott ◽

...

Keyword(s):

Gene Expression ◽

Dendritic Cells ◽

Antiviral Activity ◽

Influenza A Virus ◽

Influenza A ◽

Sendai Virus ◽

Cytokine Gene Expression ◽

Myeloid Dendritic Cells ◽

Tnf Α ◽

Alpha Beta

ABSTRACT Dendritic cells (DCs) respond to microbial infections by undergoing phenotypic maturation and by producing multiple cytokines. In the present study, we analyzed the ability of influenza A and Sendai viruses to induce DC maturation and activate tumor necrosis factor alpha (TNF-α), alpha/beta interferon (IFN-α/β), and IFN-like interleukin-28A/B (IFN-λ2/3) and IL-29 (IFN-λ1) gene expression in human monocyte-derived myeloid DCs (mDC). The ability of influenza A virus to induce mDC maturation or enhance the expression of TNF-α, IFN-α/β, interleukin-28 (IL-28), and IL-29 genes was limited, whereas Sendai virus efficiently induced mDC maturation and enhanced cytokine gene expression. Influenza A virus-induced expression of TNF-α, IFN-α, IFN-β, IL-28, and IL-29 genes was, however, dramatically enhanced when cells were pretreated with IFN-α. IFN-α priming led to increased expression of Toll-like receptor 3 (TLR3), TLR7, TLR8, MyD88, TRIF, and IFN regulatory factor 7 (IRF7) genes and enhanced influenza-induced phosphorylation and DNA binding of IRF3. Influenza A virus also enhanced the binding of NF-κB to the respective NF-κB elements of the promoters of IFN-β and IL-29 genes. In mDC IL-29 induced MxA protein expression and possessed antiviral activity against influenza A virus, although this activity was lower than that of IFN-α or IFN-β. Our results show that in human mDCs viruses can readily induce the expression of IL-28 and IL-29 genes whose gene products are likely to contribute to the host antiviral response.

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