Infection of Human Dendritic Cells by Dengue Virus Causes Cell Maturation and Cytokine Production

Ho, Ling‐Jun; Wang, Jaang-Jiun; Shaio, Men‐Fang; Kao, Chuan-Liang; Chang, Deh‐Ming; Han, Shou-Wha; Lai, Jenn‐Haung

doi:10.4049/jimmunol.166.3.1499

Cited by 281 publications

(274 citation statements)

References 75 publications

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“…3A indicate that the anti-DV IFN-g response of gd T cells is also regulated by type I IFN. However, significant amounts of type I IFN are released by purified cultures of DVinfected DC (26,34,35), so that supplementing the culture medium with type I IFN, even at doses as high as 10,000 U/ml, did not increase the anti-DV IFN-g response of purified gd T cells (Fig. 4C).…”

Section: Resultsmentioning

confidence: 99%

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Type I IFNs and IL-18 Regulate the Antiviral Response of Primary Human γδ T Cells against Dendritic Cells Infected with Dengue Virus

Tsai

Liong

Gunalan

et al. 2015

The Journal of Immunology

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Little is known about the cellular mechanisms of innate immunity against dengue virus (DV) infection. Specifically, the γδ T cell response to DV has not been characterized in detail. In this article, we demonstrate that markers of activation, proliferation, and degranulation are upregulated on γδ T cells in PBMC isolated from individuals with acute dengue fever. Primary γδ T cells responded rapidly in vitro to autologous DV-infected dendritic cells by secreting IFN-γ and upregulating CD107a. The anti-DV IFN-γ response is regulated by type I IFN and IL-18 in a TCR-independent manner, and IFN-γ secreting γδ T cells predominantly expressed IL-18Rα. Antagonizing the ATP-dependent P2X7 receptor pathway of inflammasome activation significantly inhibited the anti-DV IFN-γ response of γδ T cells. Overnight priming with IL-18 produced effector γδ T cells with significantly increased ability to lyse autologous DV-infected dendritic cells. Monocytes were identified as accessory cells that augmented the anti-DV IFN-γ response of γδ T cells. Lack of monocytes in culture is associated with lower IL-18 levels in culture supernatant and diminished production of IFN-γ by γδ T cells, whereas addition of exogenous IL-18 restored the IFN-γ response of γδ T cells in monocyte-depleted cocultures with DV-infected DC. Our results indicate that primary γδ T cells contribute to the immune response during DV infection by providing an early source of IFN-γ, as well as by killing DV-infected cells, and suggest that monocytes participate as accessory cells that sense DV infection and amplify the cellular immune response against this virus in an IL-18–dependent manner.

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Section: Resultsmentioning

confidence: 99%

“…Although DV-infected DC produce significant amounts of type I IFN (26,34,35), at levels that are not limiting for IFN-g production by gd T cells (Fig. 4C), the amount of IL-18 that is released by these infected cells is sufficient only for a basal anti-DV response.…”

Section: Discussionmentioning

confidence: 99%

Type I IFNs and IL-18 Regulate the Antiviral Response of Primary Human γδ T Cells against Dendritic Cells Infected with Dengue Virus

Tsai

Liong

Gunalan

et al. 2015

The Journal of Immunology

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“…We showed that OBP-301-infected oncolytic tumor cells efficiently stimulated immature DCs to produce greater amounts of IFN-g and IL-12 than apoptotic and necrotic cells, and that such stimulation led to DC maturation. Viral infection itself has been reported to activate DCs to secrete pro-or anti-inflammatory cytokines, which can drive DCs to undergo the maturation process (Ho et al, 2001); the observation that OBP-301 alone had no effect on cytokine production by DCs, however, indicates that OBP-301 itself may be less infective or stimulatory to DCs. The result is consistent with our finding that OBP-301 attenuated replication as well as cytotoxicity in human normal cells.…”

Section: Virus-mediated Oncolysis Y Endo Et Almentioning

confidence: 99%

Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation

et al. 2007

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Dendritic cells (DCs) are the most potent antigenpresenting cells and acquire cellular antigens and danger signals from dying cells to initiate antitumor immune responses via direct cell-to-cell interaction and cytokine production. The optimal forms of tumor cell death for priming DCs for the release of danger signals are not fully understood. OBP-301 (Telomelysin) is a telomerasespecific replication-competent adenovirus that induces selective E1 expression and exclusively kills human cancer cells. Here, we show that OBP-301 replication produced the endogenous danger signaling molecule, uric acid, in infected human tumor cells, which in turn stimulated DCs to produce interferon-c (IFN-c) and interleukin 12 (IL-12). Subsequently, IFN-c release upregulated the endogenous expression of the proteasome activator PA28 in tumor cells and resulted in the induction of cytotoxic T-lymphocytes. Our data suggest that virus-mediated oncolysis might be the effective stimulus for immature DCs to induce specific activity against human cancer cells.

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“…Human myeloid DC could be induced to mature and upregulate CD1d either directly through their own virusrecognizing pattern recognition receptors or indirectly through IFN-a released by stimulated human pDC. In addition, type I IFN is released by myeloid DC in response to viruses [62,63] and may act via a paracrine or autocrine loop [64]. As a consequence of CD1d-enhancing mechanisms, NKT cells are activated by recognition of either an endogenous, stress-induced or viral ligand.…”

Section: Discussionmentioning

confidence: 99%

Viral danger signals control CD1d de novo synthesis and NKT cell activation

et al. 2008

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The nonpolymorphic CD1 molecules present lipid antigens to T cells. In myeloid DC humans express five different CD1 proteins (CD1a-e; the corresponding CD1 genes are designated CD1A-E). A role for CD1d-restricted NKT cells in the control of virus infections has been delineated from clinical observations, mouse models and viral evasion mechanisms targeting CD1d. How NKT cells are activated by virus infections is unclear. We found that human myeloid DC differentially regulate CD1 antigen presentation in response to viral danger signals. Stimulation with type I IFN, viral TLR ligands or viruses strongly enhanced the number of CD1D transcripts in human myeloid DC but diminished the abundance of CD1A, CD1B and CD1E mRNA. These changes on the transcriptional level were mirrored by altered cellular distribution and increased surface expression of CD1d. As a consequence NKT cells were activated and showed a Th1-like response. Moreover, NKT cell activation in PBMC exposed to viral danger signals was dependent on human plasmacytoid DC which produce large amounts of IFN-a. In conclusion, our data indicate that viral danger signals trigger NKT cell activation by enhancing CD1d de novo synthesis through increasing the abundance of CD1D mRNA in human myeloid DC. IntroductionThe immune system detects viruses by recognizing antigens loaded on specialized surface molecules. The highly polymorphic MHC molecules bind to diverse peptides, traffic to the cell surface, and display this information to T cells [1]. Although distantly related to MHC proteins, the nonpolymorphic CD1 proteins constitute an evolutionarily distinct family of antigenpresenting molecules [2]. Humans express five different CD1 proteins (CD1a-e; the corresponding CD1 genes are designated CD1A-E). They are further divided into group 1 (CD1a-c) and group 2, which contains CD1d as the sole member. In contrast, CD1e is not expressed on the cell surface and is an intermediate form in terms of its homology to the other CD1 molecules. Accordingly, it is regarded as a group 3 CD1 molecule [3].By trafficking through endosomal compartments, CD1 proteins pick up antigens in a similar fashion to MHC class II molecules [4]. However, instead of peptides, CD1 molecules present lipids, glycolipids or lipopeptides of either foreign or self origin [2,5]. The CD1d-restricted NKT cells can also recognize a-galactosylceramide (aGalCer), a well-studied and highly potent CD1d ligand derived from a marine sponge [6,7]. These [18,25] or improves disease outcome [12,26]. Moreover, viruses subvert antigen presentation through CD1d [27][28][29][30][31][32][33], indicating its importance in antiviral immune defense.The mechanisms leading to activation of CD1d-restricted NKT cells in humans infected with viral pathogens are unknown. However, DC will play an important role as they link the innate and adaptive antiviral immunity [34]. DC sense invading viruses by detecting conserved pathogen-associated molecular patterns through a variety of different pattern recognition receptors, e.g. TLR...

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Infection of Human Dendritic Cells by Dengue Virus Causes Cell Maturation and Cytokine Production

Cited by 281 publications

References 75 publications

Type I IFNs and IL-18 Regulate the Antiviral Response of Primary Human γδ T Cells against Dendritic Cells Infected with Dengue Virus

Type I IFNs and IL-18 Regulate the Antiviral Response of Primary Human γδ T Cells against Dendritic Cells Infected with Dengue Virus

Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation

Viral danger signals control CD1d de novo synthesis and NKT cell activation

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