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Human Monocyte Subsets Are Transcriptionally and Functionally Altered in Aging in Response to Pattern Recognition Receptor Agonists
Journal article   Open access   Peer reviewed

Human Monocyte Subsets Are Transcriptionally and Functionally Altered in Aging in Response to Pattern Recognition Receptor Agonists

Talibah U Metcalf, Peter A Wilkinson, Mark J Cameron, Khader Ghneim, Cindy Chiang, Anne M Wertheimer, John B Hiscott, Janko Nikolich-Zugich and Elias K Haddad
The Journal of immunology (1950), v 199(4), pp 1405-1417
15 Aug 2017
DOI: https://doi.org/10.4049/jimmunol.1700148
PMID: 28696254
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc5548610View
Accepted (AM)Open Access (License Unspecified),  Open
url
https://doi.org/10.4049/jimmunol.1700148View
Published, Version of Record (VoR) Open

Abstract

Adult Aged Aged, 80 and over Aging - immunology Cytokines - biosynthesis Cytokines - genetics Cytokines - immunology Female Gene Expression Profiling GPI-Linked Proteins - analysis Humans Immunity, Innate Interferons - biosynthesis Interferons - immunology Lipopolysaccharide Receptors - analysis Male Middle Aged Monocytes - classification Monocytes - immunology Monocytes - physiology Receptors, IgG - analysis Receptors, Pattern Recognition - agonists Receptors, Pattern Recognition - genetics Receptors, Pattern Recognition - metabolism Toll-Like Receptor 4 - agonists Toll-Like Receptor 4 - immunology Toll-Like Receptor 4 - metabolism Toll-Like Receptor 7 - agonists Toll-Like Receptor 7 - immunology Toll-Like Receptor 7 - metabolism Toll-Like Receptor 8 - agonists Toll-Like Receptor 8 - immunology Toll-Like Receptor 8 - metabolism Transcription, Genetic Young Adult
Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to promote Ag presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14 CD16 ), intermediate (CD14 CD16 ), and nonclassical (CD14 CD16 ) monocytes. Monocytes sorted from nonfrail healthy adults (21-40 y) and old (≥65 y) individuals were analyzed after stimulation with TLR4, TLR7/8, and retinoic acid-inducible gene I agonists. Our data showed that under nonstimulated conditions, monocyte subsets did not reveal significant age-related alternations; however, agonist stimulated-monocytes from adults and old subjects did show differences at the transcriptional and functional levels. These alternations in many immune-related transcripts and biological processes resulted in reduced production of IFN-α, IFN-γ, IL-1β, CCL20, and CCL8, and higher expression of CX3CR1 in monocytes from old subjects. Our findings represent a comprehensive analysis of the influence of human aging on pattern recognition receptors signaling and monocyte functions, and have implications for strategies to enhance the immune response in the context of infection and immunization.

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130 citations in Web of Science
129 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
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