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Principal Investigator: Peter Deak
Organization: UNIVERSITY OF CHICAGO
Fiscal Year: 2019
Award: $61,610
Funding agency: National Institute of Allergy and Infectious Diseases
Project Abstract:
Dendritic cell (DC) antigen uptake and presentation is a crucial initial step in establishing adaptive immune
responses. This project will characterize a small sub-set of DCs, called hyper-responder DCs, which display
enhanced antigen uptake, immune activation and potentially initiate immune responses using paracrine
signaling. We will first identify these DCs by observing their uptake of fluorescently labeled, polystyrene coated
microparticles, which display toll-like-receptor (TLR) agonist molecules on their surface, and the kinetics of
hyper-responder immune activation. Next, we will establish a transcriptional profile for hyper-responders by
performing both bulk and single cell mRNA sequencing. By inhibiting cytokine release using the inhibitor
brefeldin A, we will also assess the contribution hyper-responders make to the overall immune response via
paracrine signaling and any specific genes regulated in a paracrine fashion. We will also repeat this analysis
using synergistic combination of TLR agonists in order to identify genes responsible for TLR synergy. Any
genes of interest will be validated through T cell interaction studies, western blots, flow cytometery and/or
immunofluorescent staining. By characterizing the hyper-responsive cells and their transcriptional responses
to paracrine signaling and TLR synergy, this project will advance our understanding of antigen presentation
and aid in the development of more efficacious vaccines.
Terms: <ATGN><Address><Agonist><Anti-inflammatory><Antigen Presentation><Antigens><Ascotoxin><Assay><Automobile Driving><Basal Transcription Factor><Basal transcription factor genes><Bioassay><Biologic Assays><Biologic Models><Biological Assay><Biological Models><Bone Marrow><Bone Marrow Reticuloendothelial System><Brefeldin A><CD8><CD8B><CD8B1><CD8B1 gene><Cell Body><Cell Communication><Cell Communication and Signaling><Cell Interaction><Cell Line><Cell Signaling><Cell-to-Cell Interaction><CellLine><Cells><Cyanein><Data><Decumbin><Dendritic Cells><Dendritic cell activation><Development><Drug usage><ELISA><Enzyme-Linked Immunosorbent Assay><Event><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Gene Transcription><General Transcription Factor Gene><General Transcription Factors><Genes><Genetic Transcription><Glean><Hen Egg Lysozyme><Heterogeneity><Immune response><Immunologic Subtyping><Immunological response><Immunophenotyping><Incubated><Inflammatory><Inflammatory Response><Interruption><Intracellular Communication and Signaling><Kinetics><Knowledge><LYT3><Label><Laboratories><Mediating><Messenger RNA><Methods><Mice><Mice Mammals><Microscopy><Model System><Modeling><Murine><Mus><Nuclear><Paracrine Communication><Paracrine Signaling><Pathogenicity><Peptides><Phenotype><Polystyrenes><Polystyrol><Population><Production><RNA Expression><Receptor Activation><Role><SCmRNAseq><Short interfering RNA><Signal Transduction><Signal Transduction Systems><Signaling><Small Interfering RNA><Staining method><Stains><Strains Cell Lines><Surface><Synergisidin><System><T cell activating factor><T cell response><T-Cells><T-Lymphocyte><TIL4><TLR protein><TLR2><TLR2 gene><TLR2 receptor><Testing><Toll-Like Receptor 2><Toll-Like Receptor Family Gene><Toll-like receptors><Toll/Interleukin 1 Receptor-Like 4><Toll/Interleukin 1 Receptor-Like 4 Gene><Toll/Interleukin 1 Receptor-Like Protein 4><Transcription><Transcription Factor Proto-Oncogene><Transcription factor genes><Vaccine Design><Vaccines><Validation><Veiled Cells><Western Blotting><Western Immunoblotting><adaptive immune response><antiinflammatory><base><biological signal transduction><cell type><cultured cell line><cytokine><develop a vaccine><development of a vaccine><developmental><driving><drug use><experiment><experimental research><experimental study><flow cytophotometry><gene signatures><genetic signature><host response><immune activation><immunogen><immunophenotype><immunoresponse><in vivo><inhibitor><inhibitor/antagonist><interest><knock-down><knockdown><mRNA><mRNA sequencing><mRNA-seq><novel><paracrine><pathogen><prevent><preventing><protein blotting><response><siRNA><single cell mRNA sequencing><social role><synergism><thymus derived lymphocyte><transcription factor><uptake><vaccine development><vaccine formulation>