Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen-recognition receptors

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE62627 | GEO | 2015/01/01

SECONDARY ACCESSION(S): PRJNA264572

REPOSITORIES: GEO