Toll-Like Receptor 9 in Plasmacytoid Dendritic Cells Fails To Detect Parvoviruses

Mattei, Lisa M.; Cotmore, Susan F.; Li, Lei; Tattersall, Peter; Iwasaki, Akiko

doi:10.1128/jvi.03155-12

Cited by 14 publications

(15 citation statements)

References 16 publications

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“…Although the biology for these different genera cannot be presumed to be identical, some similarities might nevertheless be expected. TLR-9 mediated an IFN response to wild-type AAV in murine and human pDCs (56), consistent with results for autonomous parvoviruses in hPBMCs (23) but in contrast to the absence of a response to MVMp seen by Mattei et al in murine pDCs (46). We found that exogenous IFN was unable to block infection of human cells by an AAV vector.…”

Section: Discussionsupporting

confidence: 71%

“…An absence of an IFN response to parvoviruses was reported in some murine cells, including A9 transformed murine fibroblasts (21) and murine plasmacytoid dendritic cells (46). Our study may be the first to investigate the IFN response to autonomous parvoviruses in a variety of normal human cells.…”

Section: Discussionmentioning

confidence: 94%

“…However, bone marrowderived murine pDCs did not respond to MVMp infection (46). Interestingly, purified naked MVMp genomic single-stranded DNA did stimulate IFN-␣ secretion in murine pDCs, suggesting MVMp capsid-mediated physical protection of the DNA genome from PRRs or capsid-mediated trafficking of viral PAMPs away from PRRs (46). Among different cell types, parvoviral DNA exposure outside the capsid may vary in degree and in location (50).…”

Section: Discussionmentioning

confidence: 99%

“…Since the only cell populations within hPBMCs known to possess functional TLR-9 pathways are B cells and plasmacytoid dendritic cells (pDCs) (48) and since B cells secrete tumor necrosis factor alpha and interleukin-6 rather than IFN upon TLR-9 stimulation (49), pDCs may be the predominant producers of the IFN response in hPBMCs (23). However, bone marrowderived murine pDCs did not respond to MVMp infection (46). Interestingly, purified naked MVMp genomic single-stranded DNA did stimulate IFN-␣ secretion in murine pDCs, suggesting MVMp capsid-mediated physical protection of the DNA genome from PRRs or capsid-mediated trafficking of viral PAMPs away from PRRs (46).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Autonomous Parvoviruses neither Stimulate nor Are Inhibited by the Type I Interferon Response in Human Normal or Cancer Cells

Paglino

Andres

Pol

2014

J Virol

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Members of the genus IMPORTANCEUnderstanding the interactions between oncolytic viruses and the innate immune system will facilitate employing these viruses as therapeutic agents in cancer patients. The cancer-selective nature of some oncolytic viruses is based on the impaired innate immunity of many cancer cells. The parvoviruses H-1, LuIII, and MVM target cancer cells; however, their relationship with the innate immune system is relatively uncharacterized. Surprisingly, we found that these parvoviruses do not evoke an interferon response in normal human fibroblasts, glia, or melanocytes. Furthermore, unlike most other types of virus, we found that parvovirus infectivity is unaffected by interferon treatment of human normal or tumor cells. Finally, parvoviral replication was unimpaired by interferon in four human tumor types, including those with residual interferon functionality. We conclude that deficits in the interferon antiviral response of cancer cells do not contribute to parvoviral oncoselectivity in human cells. The interferon-resistant phenotype of parvoviruses may give them an advantage over interferon-sensitive oncolytic viruses in tumors showing residual interferon functionality.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Autonomous Parvoviruses neither Stimulate nor Are Inhibited by the Type I Interferon Response in Human Normal or Cancer Cells

Paglino

Andres

Pol

2014

J Virol

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“…Lysosomal and cytoplasmic sensors binding viral RNA (TLR3, protein kinase R [PKR], RIG-I, and MAVS) or ssDNA (TLR9) sequences have been shown to respond to infection with the autonomous parvoviruses MVMp and H-1PV (36,44,(97)(98)(99)(100). Notably, the cell-type-dependent pattern of sensor expression determined both induction of the IFN response and permissiveness for virus infection, accounting for the abortion of the viral life cycle in TLR3/TLR9/PKR-positive fibroblasts or immune cells and for the success of virus replication in tumor cells lacking these intracellular receptors.…”

Section: Discussionmentioning

confidence: 99%

Complementary Induction of Immunogenic Cell Death by Oncolytic Parvovirus H-1PV and Gemcitabine in Pancreatic Cancer

Angelova

Grekova

Heller

et al. 2014

J Virol

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Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease, with a median survival time of less than 9 months and a 5-year survival rate of Ͻ1%. Current advances in surgical, (neo)adjuvant, and palliative treatments have failed to prevent recurrence and ultimate metastasis (1-3).In order to be effective, chemotherapy must reduce the tumor burden, promote anticancer immunity, and alleviate intratumoral immunosuppression (4-6). Forced tumor cell death in an immunogenic manner (i.e., immunogenic cell death [ICD]) has been proposed as the best way to trigger an adaptive immune response, boosting the therapeutic efficacy of a cytoreductive treatment (7,8). Preapoptotic surface exposure of calreticulin (CRT) (as a result of the endoplasmic reticulum stress response), as well as release of ATP (autophagy) and high-mobility group box B1 protein (HMGB1) (late apoptosis/necrosis), is considered the optimal ICD combination for dying tumor cells to enable paracrine activation of dendritic cells and the consequent priming of cytotoxic effectors. The surface exposure of CRT promotes uptake of dying tumor cells by dendritic cells, and the release of HMGB1 engages

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Bacterium‐Mimicking Vector with Enhanced Adjuvanticity for Cancer Immunotherapy and Minimized Toxicity

Zheng

Chen

et al. 2019

Adv Funct Materials

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Bacteria are utilized as adjuvants for anticancer immunotherapy. However, immunotherapy with bacteria or their extracts is limited due to their toxicity. On the basis of the innate molecular interactions of foreign molecules from the bacterial components with the host pattern recognition receptors (PRRs), a synthetic adjuvant vector morphologically mimicking the bacterium is engineered, which comprises an optimal combination of components derived from bacterial cell wall, flagellum, and nucleoid. The bacterium-mimicking vectors (BMVs) cooperatively trigger multiple signaling pathways of PRRs and display superior antitumor therapeutic and prophylactic effects to either that of the reported synthetic or bacterium-derived adjuvant. Significantly, BMVs improve the efficacy of photothermal ablation therapy to eradicate 50% of large established tumor in mice that completely reject tumor rechallenge. The synthetic BMVs with the detoxified and controllable composition exhibit minimized toxicity. Such a bacterium-mimicking engineering strategy provides a rational approach to select pathogen-associated molecular patterns, which drives the desired antitumor immune response. The engineered BMVs offer a promising alternative to the bacterial adjuvant for cancer immunotherapy.

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Toll-Like Receptor 9 in Plasmacytoid Dendritic Cells Fails To Detect Parvoviruses

Cited by 14 publications

References 16 publications

Autonomous Parvoviruses neither Stimulate nor Are Inhibited by the Type I Interferon Response in Human Normal or Cancer Cells

Autonomous Parvoviruses neither Stimulate nor Are Inhibited by the Type I Interferon Response in Human Normal or Cancer Cells

Complementary Induction of Immunogenic Cell Death by Oncolytic Parvovirus H-1PV and Gemcitabine in Pancreatic Cancer

Bacterium‐Mimicking Vector with Enhanced Adjuvanticity for Cancer Immunotherapy and Minimized Toxicity

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