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

Journal of Immunology - Tập 199 Số 4 - Trang 1405-1417 - 2017
Talibah Metcalf1, Peter Wilkinson2, Mark J. Cameron3, Khader Ghneim2, Cindy Chiang4, Anne M. Wertheimer5,6, John Hiscott7, Janko Nikolich‐Žugich5,6, Elias K. Haddad1
1*Division of Infectious Diseases and HIV Medicine, Department of Medicine, Drexel University, Philadelphia, PA 19102;
2Department of Pathology, Case Western Reserve University, Cleveland, OH 44106
3Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106
4§Department of Microbiology, University of Chicago, Chicago, IL 60637;
5¶Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ 85724;
6‖Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724; and
7#Laboratorio Pasteur, Istituto Pasteur-Fondazione Cenci Bolognetti, 00161 Rome, Italy

Tóm tắt

AbstractAge-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 (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-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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Journal of Immunology

Tập 199 Số 4

1405-1417

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