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, Elias K. Haddad

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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+CD162), intermediate (CD14+CD16+), and nonclassical (CD14dimCD16+) 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-a, IFN-γ, IL-1b, 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.

Original languageEnglish (US)
Pages (from-to)1405-1417
Number of pages13
JournalJournal of Immunology
Volume199
Issue number4
DOIs
StatePublished - Aug 15 2017

ASJC Scopus subject areas

  • Immunology

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