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Title: Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen-recognition receptors      
keywords:
Transcriptome or Gene expression
ID:
PRJNA264572
description:
Aging leads to dysregulation of multiple components of the immune system that result in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive T- and B-cells are well documented but the effect of aging on innate immunity remains incompletely understood. Therefore, we first undertook transcriptional profiling of peripheral blood mononuclear cells (PBMCs) and found that PBMCs isolated from old individuals (≥65 yrs) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤40 yrs). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2 and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. We observed old PBMCs had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells and increased expression of PD-L2 and B7-H4 on B cells. The defective innate immune response adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects’ elicited significantly lower levels of adult T cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression, could be responsible for the blunt memory B and T cell immune responses to vaccines and infections. Overall design: PBMCs were treated with TLR and RIG-I agonists as follows: LPS-TLR4 (0.5 µg/ml) or CLO97-TLR7/8 (0.5 µg/ml) or poly I:C/Lyovec-RIGI/MDA5 (2 µg/ml) or 5’-pppRNA/Lyovec-RIG-I (400 ng/ml). PBMCs were cultured for 6 and 24 hrs at 37C in a 5% CO2-humidified environment.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA264572
authentication:
none
authorization:
none
ID:
pmid:25728020
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject