Delineate innate immune responses in populations at risk (the elderly and the immunosuppressed) that are different from the general population

Title:

Delineate innate immune responses in populations at risk (the elderly and the immunosuppressed) that are different from the general population

Dataset

identifier:	SDY40
description:	We will recruit adult (21-49 years of age), elderly (>50 years), ages as outlined in the RFA, or non-elderly but immunosuppressed (defined as taking at least 10 mg of prednisone daily for at least one month) participants from the Greater New Haven area and rheumatology clinics in the Yale-New Haven Healthcare System. Individuals of either gender and all ethnic groups will be eligible to participate. We will stimulate monocytes and DCs in vitro with ligands of TLRs 1-9 and quantify the efficiency of stimulation by assessment of production of cytokines and inflammatory mediators. TLRs 10 and 11 will not be addressed at this time as ligands are not known. Lineage specific pro-inflammatory cytokines from PBMCs by FACs. We will quantify intracellular levels of TNFα and IL-6 by FACS from PBMCs in suspension on the day of isolation of the cells. This is essential to control for differences in cell composition in PBMCs isolated from different individuals, given the broad range of hematopoietic cells synthesizing TNFα and IL-6. By using multi-color staining of PBMCs with lineage-specific fluorescent antibodies, we will identify lineages positive for intracellular cytokine production at the single cell level, and track potential age-associated changes in cell lineages. Our experimental approach will be to obtain monocytes/macrophages cells from young adult and elderly subjects, define their Mif genotype, and analyze their baseline and stimulus-induced production of MIF. Patient samples for genotyping will be obtained from the pellet of the Ficoll-hypaque isolation of PBMCs and extracted DNA will be analyzed for Mif genotype by established, robotic methodology that requires <1 μg of DNA. Purified monocytes/macrophage will be studied for their baseline and stimulation-induced responses following protocols in place in our laboratory.
aggregation:	instance of dataset
refinement:	2 - Complete set of descriptive data and results, as ascertained by ImmPort.
availability:	available with registration
primaryPublications:	21050124 17909632 20100933 17202359 22023165 20667703 20818395 20404807 18508883 19541535 18256150 19816558 21398396 20596538 18632868 17471428 18690214 19346297 19200759 17767688 18355125 18056386
isAbout:	Assess the efficiency of the immune response of monocytes and dendritic cells in different populations (adult, elderly, immunosuppressed) in response to stimulation with specific TLR ligands. Quantify TLR expression as well as efficiency of signaling pathways triggered by TLR engagement to identify mechanisms that contribute to the impairments of innate immunity associated with aging and immunosuppression. Assess the functional and genetic polymorphisms of MIF in the innate response to TLR stimulation.

Access

authorizations:	registration required
accessURL:	https://aspera-immport.niaid.nih.gov:9443/browser?path=SDY40
landingPage:	http://www.immport.org/immport-open/public/study/study/displayStudyDetail/SDY40

Dimension

clinical trial:
study category:	Infection Response
study type:	Observational
subject species:	Homo sapiens
biosample type:	Other
subject gender:	Both
assay type:	ELISA Flow Cytometry PCR Q-PCR Western Blot

Disease

name:	West Nile Virus, Immune response, Aging, Infectious diseases

Person

fullName:	Erol Fikrig
affiliations:	Yale School of Medicine
roles:	principal investigator

Study Group

name:	Delineate innate immune responses in populations at risk (the elderly and the immunosuppressed) that are different from the general population
size:	903

Study

name:	Innate Immune Responsiveness in the Elderly and the Immunosuppressed
output:	Stimulate pro-inflammatory cytokines through TLR ligands. Measurement of cytokine production from lineage specific pro-inflammatory cytokines from PBMCs by FACs. Quantify surface expression and mRNA levels of TLRs in PBMCs by FACS and Q-PCR. Effects of aging and immunosuppression on production of MIF by Monocytes and analysis of MIF promoter polymorphisms. Assess the signaling pathways in response to TLR ligands.
studyGroups:	Young Adults: Healthy subjects between the ages of 21 to 49 years old. Elderly: Elderly subjects 50 years of age or older. Immunocompromised: Immunocompromised subjects.
description:	We will assess the efficiency of the immune response of monocytes and dendritic cells in different populations (young adult and elderly) in response to stimulation with specific TLR ligands. We will focus separately on TLRs 3, 7, 8, 9, that recognize viral targets, TLRs 1, 2, 4, 6 (bacterial targets), and the effects of aging on MIF. We will quantify TLR expression as well as efficiency of signaling pathways triggered by TLR engagement to identify mechanisms that contribute to the impairments of innate immunity associated with aging and immunosuppression. Finally, we will assess the functional and genetic polymorphisms of MIF in the innate response to TLR stimulation.
identifier:	10.21430/M3EMF3OMS4

Data Repository

name:	ImmPort
identifier:	SCR:012804
homePage:	http://www.immport.org

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