hDectin-1 Is Involved in the Uptake of Apoptotic and Infected Cells and Mediates Cross-Presentation of Engulfed Antigens.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3086-3086
Author(s):  
Markus M. Weck ◽  
Frank Grünebach ◽  
Daniela Werth ◽  
Lothar Kanz ◽  
Christian Sinzger ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mammalian Cells ◽  
Specific Binding ◽  
Human Tumor ◽  
Extracellular Domain ◽  
Poly I:C ◽  
Cross Presentation ◽  
Infected Cells ◽  
Stimulation Of

Abstract Dectin-1 is a member of the c-type-lectin-like receptor family that was shown to be the major receptor for fungal beta-glucans and to play an important role in the cellular responses mediated by these carbohydrates. In the present study we identified the hDectin-1b splice variant as the major isoform expressed in in vitro generated mDC using a quantitative RT-PCR and western blot analysis. Interestingly, stimulation of immature DC with the toll like receptor ligands Poly I:C (TLR3) or LPS (TLR4) but not with TLR ligands 2 and 7 or TNF-a led to a dramatic down regulation of hDectin-1 protein expression. To further analyze the possible involvement of Dectin-1 in the phagocytosis of cellular material we recombinantly expressed the extracellular domain (ECD) of hDectin-1b and used it to stain tumor cells. The recombinant ECD showed a specific binding to several human tumor cell lines that could be increased by induction of apoptosis in malignant cells and inhibited by incubation of the extracellular domain with zymosan, a crude cell wall extract of saccharomyces cerevisiae. Furthermore, uptake of tumor cells by immature mDC was reduced by zymosan or the presence of the recombinant Dectin-1 in phagocytosis assays suggesting that Dectin-1 is involved in the engulfement of tumor cells by DC. In line with the expression analysis of hDectin-1, we found that phagocytosis of apoptotic cells was dramatically reduced upon stimulation of DCs with Poly I:C or LPS as compared to immature DC or DC activated with TLR2 or 7 ligands. We next analysed the role of Dectin-1 in the cross-presentation of cell derived antigens and used DC that were incubated with CMV infected fibroblasts and an autologous CTL line specific for the HLA-A2 binding pp65 peptide. Stimulation of CMV peptide specific CTL in ELIspot assays by DC that were incubated with CMV infected fibroblasts efficiently stimulated IFN-gamma secretion that could be inhibited by zymosan and the extracellular domain of Dectin-1. In line with the results from phagocytosis assays stimulation of CMV specific CTL was reduced by stimulation of DC with TLR2 and 4 ligands. Our results identify hDectin-1 as a new receptor for endogenous ligands on mammalian cells and indicate an important role of this molecule in the clearing of apoptotic and infected cells and cross-presentation of cell derived antigens..

scholarly journals Vpr Enhances Tumor Necrosis Factor Production by HIV-1-Infected T Cells

2015 ◽  
Vol 89 (23) ◽  
pp. 12118-12130 ◽  
Author(s):  
Ferdinand Roesch ◽  
Léa Richard ◽  
Réjane Rua ◽  
Françoise Porrot ◽  
Nicoletta Casartelli ◽  
...  
Keyword(s):  
Immune Responses ◽  
Proinflammatory Cytokine ◽  
Tumor Necrosis ◽  
Cellular Proteins ◽  
Accessory Protein ◽  
Infected Cells ◽  
Hiv 1 ◽  
Necrosis Factor ◽  
Stimulation Of

ABSTRACTThe HIV-1 accessory protein Vpr displays different activities potentially impacting viral replication, including the arrest of the cell cycle in the G2phase and the stimulation of apoptosis and DNA damage response pathways. Vpr also modulates cytokine production by infected cells, but this property remains partly characterized. Here, we investigated the effect of Vpr on the production of the proinflammatory cytokine tumor necrosis factor (TNF). We report that Vpr significantly increases TNF secretion by infected lymphocytes.De novoproduction of Vpr is required for this effect. Vpr mutants known to be defective for G2cell cycle arrest induce lower levels of TNF secretion, suggesting a link between these two functions. Silencing experiments and the use of chemical inhibitors further implicated the cellular proteins DDB1 and TAK1 in this activity of Vpr. TNF secreted by HIV-1-infected cells triggers NF-κB activity in bystander cells and allows viral reactivation in a model of latently infected cells. Thus, the stimulation of the proinflammatory pathway by Vpr may impact HIV-1 replicationin vivo.IMPORTANCEThe role of the HIV-1 accessory protein Vpr remains only partially characterized. This protein is important for viral pathogenesis in infected individuals but is dispensable for viral replication in most cell culture systems. Some of the functions described for Vpr remain controversial. In particular, it remains unclear whether Vpr promotes or instead prevents proinflammatory and antiviral immune responses. In this report, we show that Vpr promotes the release of TNF, a proinflammatory cytokine associated with rapid disease progression. Using Vpr mutants or inhibiting selected cellular genes, we show that the cellular proteins DDB1 and TAK1 are involved in the release of TNF by HIV-infected cells. This report provides novel insights into how Vpr manipulates TNF production and helps clarify the role of Vpr in innate immune responses and inflammation.

Growth Factor-Dependent Stimulation of Primary Human Tumor Cells

1990 ◽  
pp. 173-180
Author(s):  
H. Depenbrock ◽  
J. Trijssenaar ◽  
D. Neukam ◽  
H.-J. Meyer ◽  
M. Freund ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Human Tumor ◽  
Human Tumor Cells ◽  
Stimulation Of

scholarly journals In vivo invasion of modified chorioallantoic membrane by tumor cells: the role of cell surface-bound urokinase.

1988 ◽  
Vol 107 (6) ◽  
pp. 2437-2445 ◽  
Author(s):  
L Ossowski
Keyword(s):  
Cell Surface ◽  
Plasminogen Activator ◽  
Tumor Cells ◽  
Chorioallantoic Membrane ◽  
Human Tumor ◽  
Chick Embryo Chorioallantoic Membrane ◽  
Catalytically Active ◽  
Surface Receptor

The ability of the chick embryo chorioallantoic membrane (CAM) to withstand invasion by tumor cells can be intentionally compromised by altering its morphological integrity. Using a newly developed quantitative assay of invasion we showed that intact CAMs were completely resistant to invasion by tumor cells, wounded CAMs did not pose a barrier to penetration, and CAMs that were wounded and then allowed to reseal displayed partial susceptibility to invasion. The invasion of resealed CAMs required catalytically active plasminogen activator (PA) of the urokinase type (uPA); the invasive efficiency of tumor cells was reduced by 75% when tumor uPA activity or tumor uPA production was inhibited. The invasive ability of human tumor cells, which have surface uPA receptors but which do not produce the enzyme, could be augmented by saturating their receptors with exogenous uPA. The mere stimulation of either uPA or tissue plasminogen activator production, in absence of binding to cell receptors, did not result in an enhancement of invasiveness. These findings suggest that the increased invasive potential of tumor cells is correlated with cell surface-associated proteolytic activity stemming from the interaction between uPA and its surface receptor.

scholarly journals Binding of cellular p32 protein to the rubella virus P150 replicase protein via PxxPxR motifs

2012 ◽  
Vol 93 (4) ◽  
pp. 807-816 ◽  
Author(s):  
Suganthi Suppiah ◽  
Heather A. Mousa ◽  
Wen-Pin Tzeng ◽  
Jason D. Matthews ◽  
Teryl K. Frey
Keyword(s):  
Rubella Virus ◽  
Rna Synthesis ◽  
Specific Binding ◽  
Infectious Clone ◽  
Binding Motifs ◽  
Replicase Protein ◽  
Virus Rna ◽  
Infected Cells ◽  
Proline Rich Region

A proline-rich region (PRR) within the rubella virus (RUBV) P150 replicase protein that contains three SH3 domain-binding motifs (PxxPxR) was investigated for its ability to bind cell proteins. Pull-down experiments using a glutathione S-transferase–PRR fusion revealed PxxPxR motif-specific binding with human p32 protein (gC1qR), which could be mediated by either of the first two motifs. This finding was of interest because p32 protein also binds to the RUBV capsid protein. Binding of p32 to P150 was confirmed and was abolished by mutation of the first two motifs. When mutations in the first two motifs were introduced into a RUBV cDNA infectious clone, virus replication was significantly impaired. However, virus RNA synthesis was found to be unaffected, and subsequent immunofluorescence analysis of RUBV-infected cells revealed co-localization of p32 and P150 but little overlap of p32 with RNA replication complexes, indicating that p32 does not participate directly in virus RNA synthesis. Thus, the role of p32 in RUBV replication remains unresolved.

Role of interferon-activated macrophages in eradication of human tumor cells by innate immunity

Cytokine ◽  
2009 ◽  
Vol 48 (1-2) ◽  
pp. 48
Author(s):  
Samuel Baron ◽  
Julie Horowitz ◽  
Joyce Poast ◽  
Angel Morrow ◽  
Samuel Fey ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Tumor Cells ◽  
Human Tumor ◽  
Activated Macrophages ◽  
Human Tumor Cells

scholarly journals Human neutrophil-mediated lysis of ovarian cancer cells

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 805-809 ◽  
Author(s):  
A Lichtenstein ◽  
M Seelig ◽  
J Berek ◽  
J Zighelboim
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cells ◽  
Human Tumor ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Myristate Acetate ◽  
Human Tumor Cells ◽  
Effector Cells ◽  
Lethal Event ◽  
Stimulation Of

Abstract Because of recent questions concerning the sensitivity of human tumor cells to neutrophil-induced oxidative injury, we studied six freshly obtained human ovarian cancer (OC) specimens. Stimulation of neutrophils (PMNs) by phorbol myristate acetate (PMA) did not result in OC cytolysis during the first nine hours of incubation. However, three of six specimens were significantly lysed by stimulated PMNs when assay length was increased to 18 hours. Cytotoxicity was mediated by PMN production of reactive oxidative intermediates (ROIs). Presentation of ROIs to OC targets as preformed or enzymatically generated molecules in cell-free systems duplicated the enhanced lysis at 18 hours (as compared with six hours). Since addition of catalase at three or six hours did not inhibit enhanced lysis at 18 hours (achieved by PMNs or in cell-free systems), it appears that an initial ROI-mediated lethal event occurs early, but longer incubations are required for the event to become manifested as cell death. These data suggest that shorter assays may underestimate the potential of PMNs as effector cells against human tumor cells.

scholarly journals Antiviral Role of IFITM Proteins in Classical Swine Fever Virus Infection

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 126 ◽  
Author(s):  
Cheng Li ◽  
Hongqing Zheng ◽  
Yifan Wang ◽  
Wang Dong ◽  
Yaru Liu ◽  
...  
Keyword(s):  
Classical Swine Fever Virus ◽  
Mammalian Cells ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Late Endosomes ◽  
Early Endosomes ◽  
Infected Cells ◽  
The Relationship ◽  
Antiviral Role

The proteins IFITM1, IFITM2, and IFITM3 are host effectors against a broad range of RNA viruses whose roles in classical swine fever virus (CSFV) infection had not yet been reported. We investigated the effect of these proteins on CSFV replication in mammalian cells. The proteins were overexpressed and silenced using lentiviruses. Confocal microscopy was used to determine the distribution of these proteins in the cells, and immunofluorescence colocalization analysis was used to evaluate the relationship between IFITMs and the CSFV endosomal pathway, including early endosomes, late endosomes, and lysosomes. IFITM1, IFITM2, or IFITM3 overexpression significantly inhibited CSFV replication, whereas protein knockdown enhanced CSFV replication. In porcine alveolar macrophages (PAMs), IFITM1 was mainly located at the cell surface, whereas IFITM2 and IFITM3 were mainly located in the cytoplasm. Following CSFV infection, the distribution of IFITM1 changed. IFITM1, IFITM2, and IFITM3 colocalization with Lamp1, IFITM2 with Rab5 and Rab7, and IFITM3 with Rab7 were observed in CSFV-infected cells. Collectively, these results provide insights into the possible mechanisms associated with the anti-CSFV action of the IFITM family.

scholarly journals Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohamed Helal ◽  
Chuan Yan ◽  
Zhiuyan Gong
Keyword(s):  
Tumor Cells ◽  
Proliferative Response ◽  
Gene Expression Analysis ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Secreted Factors ◽  
Sphingosine 1 Phosphate ◽  
Dependent Pathway ◽  
Stimulation Of

AbstractIt has been well known that tumor progression is dependent on secreted factors not only from tumor cells but also from other surrounding non-tumor cells. In the current study, we investigated the role of cholangiocytes during hepatocarcinogenesis following induction of oncogenic krasV12 expression in hepatocytes using an inducible transgenic zebrafish model. Upon induction of carcinogenesis in hepatocytes, a progressive cell proliferation in cholangiocytes was observed. The proliferative response in cholangiocytes was induced by enhanced lipogenesis and bile acids secretion from hepatocytes through activation of Sphingosine 1 phosphate receptor 2 (S1pr2), a known cholangiocyte receptor involving in cholangiocyte proliferation. Enhancement and inhibition of S1pr2 could accelerate or inhibit cholangiocyte proliferation and hepatocarcinogenesis respectively. Gene expression analysis of hepatocytes and cholangiocytes showed that cholangiocytes stimulated carcinogenesis in hepatocytes via an inflammatory cytokine, Il17a/f1, which activated its receptor (Il17ra1a) on hepatocytes and enhanced hepatocarcinogenesis via an ERK dependent pathway. Thus, the enhancing effect of cholangiocytes on hepatocarcinogenesis is likely via an inflammatory loop.

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