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Articles 1 - 8 of 8
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Hiv-1 Selectively Infects A Subset Of Nonmaturing Bdca1-Positive Dendritic Cells In Human Blood, Angela Granelli-Piperno, Irina Shimeliovich, Margit D. Witmer-Pack
Hiv-1 Selectively Infects A Subset Of Nonmaturing Bdca1-Positive Dendritic Cells In Human Blood, Angela Granelli-Piperno, Irina Shimeliovich, Margit D. Witmer-Pack
Publications
The infection of cultured monocyte-derived dendritic cells (DCs) with HIV-1 involves CD4 and CCR5 receptors, while transmission to T cells is enhanced at least in part by the lectin DC-SIGN/CD209. In the present study, we studied BDCA-1+ myeloid DCs isolated directly from human blood. These cells express CD4 and low levels of CCR5 and CXCR4 coreceptors, but not DC-SIGN. The myeloid DCs replicate two R5 viruses, BaL and YU2, and transfer infection to activated T cells. The virus productively infects a small fraction of the blood DCs that fail to mature in culture, as indicated by the maturation markers …
A Dominant Complement Fixation Pathway For Pneumococcal Polysaccharides Initiated By Sign-R1 Interacting With C1q, Youngsun Kang, Yoonkyung Do, Haekyung Lee
A Dominant Complement Fixation Pathway For Pneumococcal Polysaccharides Initiated By Sign-R1 Interacting With C1q, Youngsun Kang, Yoonkyung Do, Haekyung Lee
Publications
The intricate system of serum complement proteins provides resistance to infection. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial binding C3 fragments recognized by leukocytes. The spleen and C3 provide resistance against blood-borne S. pneumoniae infection. To better understand the mechanisms involved, we studied SIGN-R1, a lectin that captures microbial polysaccharides in spleen. Surprisingly, conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on …
Antigen Targeting To Dendritic Cells Elicits Long-Lived T Cell Help For Antibody Responses, Silvia B. Boscardin, Julius C.R. Hafalla, Revati F. Masilamani
Antigen Targeting To Dendritic Cells Elicits Long-Lived T Cell Help For Antibody Responses, Silvia B. Boscardin, Julius C.R. Hafalla, Revati F. Masilamani
Publications
Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas humoral responses to most antigens require further collaboration between primed, antigen-specific helper T cells and naive or memory B cells. To determine whether antigens delivered to DCs in lymphoid organs induce T cell help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), to DCs in the presence of a maturation stimulus and assayed for antibodies to a hapten, (4-hydroxy-3-nitrophenyl) acetyl (NP), after boosting with OVA-NP. A single DC-targeted immunization elicited long-lived …
Intensified And Protective Cd4+ T Cell Immunity In Mice With Anti-Dendritic Cell Hiv Gag Fusion Antibody Vaccine, Christine Trumpfheller, Jennifer S. Finke, Carolina B. López
Intensified And Protective Cd4+ T Cell Immunity In Mice With Anti-Dendritic Cell Hiv Gag Fusion Antibody Vaccine, Christine Trumpfheller, Jennifer S. Finke, Carolina B. López
Publications
Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205-targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high …
Immunogenicity And Efficacy Of Immunodeficiency Virus-Like Particles Pseudotyped With The G Protein Of Vesicular Stomatitis Virus, Seraphin Kuate, Christiane P. Stahl-Hennig, Heribert Stoiber
Immunogenicity And Efficacy Of Immunodeficiency Virus-Like Particles Pseudotyped With The G Protein Of Vesicular Stomatitis Virus, Seraphin Kuate, Christiane P. Stahl-Hennig, Heribert Stoiber
Publications
Vaccination with exogenous antigens such as recombinant viral proteins, immunodeficiency virus-derived whole inactivated virus particles, or virus-like particles (VLP) has generally failed to provide sufficient protection in animal models for AIDS. Pseudotyping VLPs with the vesicular stomatitis virus G protein (VSV-G), which is known to mediate entry into dendritic cells, might allow more efficient stimulation of immune responses. Therefore, we pseudotyped noninfectious immunodeficiency virus-like particles with VSV-G and carried out a preliminary screen of their immunogenicity and vaccination efficacy. Incorporation of VSV-G into HIV-1 VLPs led to hundred-fold higher antibody titers to HIV-1 Gag and enhancement of T cell responses …
Glycolipid Α-C-Galactosylceramide Is A Distinct Inducer Of Dendritic Cell Function During Innate And Adaptive Immune Responses Of Mice, Shinichiro Fujii, Kanako Shimizu, Hiroaki Hemmi
Glycolipid Α-C-Galactosylceramide Is A Distinct Inducer Of Dendritic Cell Function During Innate And Adaptive Immune Responses Of Mice, Shinichiro Fujii, Kanako Shimizu, Hiroaki Hemmi
Publications
α-Galactosylceramide (α-GalCer) is the prototype compound for studying the presentation of glycolipids on CD1d molecules to natural killer T (NKT) lymphocytes. A single i.v. dose of glycolipid triggers a cascade of events involving the production of several cytokines over the course of a day, a short-lived activation of NKT and natural killer (NK) cells, and a more prolonged adaptive T cell immune response if certain antigens are given together with α-GalCer. We find that a recently described analogue, α-C-galactosylceramide (α-C-GalCer), more potently induces these innate and adaptive immune responses in mice. α-C-GalCer acts as a more effective trigger for IL-12 …
Apobec3g/3f Mediates Intrinsic Resistance Of Monocyte-Derived Dendritic Cells To Hiv-1 Infection, Marjorie Pion, Angela Granelli-Piperno, Bastein Mangeat
Apobec3g/3f Mediates Intrinsic Resistance Of Monocyte-Derived Dendritic Cells To Hiv-1 Infection, Marjorie Pion, Angela Granelli-Piperno, Bastein Mangeat
Publications
HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA-mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5α, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of …
Dendritic Cell Targeting Of Survivin Protein In A Xenogeneic Form Elicits Strong Cd4+ T Cell Immunity To Mouse Survivin, Anna Charalambous, Margarita Oks, Godwin W. Nchinda
Dendritic Cell Targeting Of Survivin Protein In A Xenogeneic Form Elicits Strong Cd4+ T Cell Immunity To Mouse Survivin, Anna Charalambous, Margarita Oks, Godwin W. Nchinda
Publications
To determine whether strong CD4+ T cell immunity could be induced to a nonmutated self protein that is important for tumorigenesis, we selectively targeted the xenogencic form of survivin, a survival protein overexpressed in tumors, to maturing dendritic cells in lymphoid tissues. Dendritic cell targeting via the DEC205 receptor in the presence of anti-CD40 and poly(I:C) as maturation stimuli, induced strong human and mouse survivin-specific CD4+ T cell responses, as determined by IFN-γ, TNF-α, and IL-2 production, as well as the development of lytic MHC class II-restricted T cells and memory. Immunity was enhanced further by depletion of …