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

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 re...

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Bibliographic Details
Published in:	The Journal of immunology (1950) 2017-08, Vol.199 (4), p.1405-1417
Main Authors:	Metcalf, Talibah U, Wilkinson, Peter A, Cameron, Mark J, Ghneim, Khader, Chiang, Cindy, Wertheimer, Anne M, Hiscott, John B, Nikolich-Zugich, Janko, Haddad, Elias K
Format:	Article
Language:	eng
Subjects:	Adult Adults Aged Aged, 80 and over Aging Aging - immunology Alternations Antigen presentation Biological activity CCL20 protein CD14 antigen CD16 antigen CX3CR1 protein Cytokines - biosynthesis Cytokines - genetics Cytokines - immunology Female Gene Expression Profiling GPI-Linked Proteins - analysis Humans IL-1β Immune response Immune system Immunity, Innate Immunization Impact analysis Infections Interferon Interferons - biosynthesis Interferons - immunology Lipopolysaccharide Receptors - analysis Male Middle Aged Monocytes Monocytes - classification Monocytes - immunology Monocytes - physiology Pattern recognition Peripheral blood Receptors, IgG - analysis Receptors, Pattern Recognition - agonists Receptors, Pattern Recognition - genetics Receptors, Pattern Recognition - metabolism Retinoic acid TLR4 protein TLR7 protein 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 Toll-like receptors Transcription Transcription, Genetic Vaccines Young Adult γ-Interferon
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Summary:	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.
ISSN:	0022-1767 1550-6606