Journal article
Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors
Aging cell, v 14(3), pp 421-432
Jun 2015
PMID: 25728020
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). 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. PBMCs from old subjects also 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 immune response to innate agonists 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 contribute to the blunted memory B- and T-cell immune responses to vaccines and infections.
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Details
- Title
- Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors
- Creators
- Talibah U Metcalf - Vaccine & Gene Therapy Institute of FloridaRafael A Cubas - Vaccine & Gene Therapy Institute of FloridaKhader Ghneim - Case Western Reserve UniversityMichael J CartwrightJulien Van GrevenyngheJustin M Richner - Washington University in St. LouisDavid P Olagnier - Vaccine & Gene Therapy Institute of FloridaPeter A WilkinsonMark J Cameron - Case Western Reserve UniversityByung S ParkJohn B Hiscott - Vaccine & Gene Therapy Institute of FloridaMichael S DiamondAnne M Wertheimer - University of ArizonaJanko Nikolich-Zugich - University of ArizonaElias K Haddad
- Publication Details
- Aging cell, v 14(3), pp 421-432
- Publisher
- Wiley
- Grant note
- F32 AG043223 / NIA NIH HHS N01-A1 00017 / PHS HHS HHSN272201100017C / PHS HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Physician Assistant; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000353689400013
- Scopus ID
- 2-s2.0-84927711067
- Other Identifier
- 991020100199104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology
- Geriatrics & Gerontology