Impaired Functions of Peripheral Blood Monocyte Subpopulations in Aged Humans
Open Access
- 12 August 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Clinical Immunology
- Vol. 30 (6), 806-813
- https://doi.org/10.1007/s10875-010-9448-8
Abstract
Aging is associated with increased susceptibility to microbial infections, and monocytes play an important role in microbial defense. In this study, we have identified and compared four subpopulations of monocytes (CD14++(high)CD16−, CD14+(low)CD16−, CD14++(high)CD16+, and CD14+(low)CD16+) in the peripheral blood of young and aged subjects with regard to their numbers, cytokine production, TLR expression, and phosphorylation of ERK1/2 in response to pam3Cys a TLR-1/2 ligand. Proportions and numbers of CD14++(high)CD16+ and CD14+(low)CD16+ monocytes were significantly increased, whereas proportions of CD14+(low)CD16− monocytes were decreased in aged subjects as compared to young subjects. In aged subjects, IL-6 production by all four subsets of monocytes was significantly decreased, whereas TNF-α production was decreased in monocyte subsets, except the CD14+(low)CD16− subset. A significantly reduced expression of TLR1 was observed in CD14++(high)CD16+ and CD14+(low)CD16+ monocyte subsets in aged subjects. Furthermore, following pam3Cys stimulation, ERK1/2 phosphorylation was significantly lower in CD14+(low)CD16+, CD14++(high)CD16+, and CD14+(low)CD16− subsets of monocytes from aged subjects. This is the first study of four subpopulations of monocytes in aging, which demonstrates that their functions are differentially impaired with regard to the production of cytokines, expression of TLR, and signaling via the ERK–MAPK pathway. Finally, changes in the number of monocyte subsets, and impairment of TLR1 expression, TNF-α production, and EK1/2 phosphorylation was more consistent in CD16+ monocyte subsets regardless of expression of CD14high or CD14+low, therefore highlighting the significance of further subdivision of monocytes into four subpopulations.This publication has 31 references indexed in Scilit:
- Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stageJournal of Leukocyte Biology, 2009
- Mechanisms of immunosenescenceImmunity & Ageing, 2009
- Monocyte-Mediated Defense Against Microbial PathogensAnnual Review of Immunology, 2008
- TLR signalingSeminars in Immunology, 2007
- The CD14+ CD16+ blood monocytes: their role in infection and inflammationJournal of Leukocyte Biology, 2006
- Toll-like receptor control of the adaptive immune responsesNature Immunology, 2004
- Age-related changes in lymphocyte development and functionNature Immunology, 2004
- Role of Toll-Like Receptors in Pathogen RecognitionClinical Microbiology Reviews, 2003
- Blood Monocytes Consist of Two Principal Subsets with Distinct Migratory PropertiesImmunity, 2003
- Clinical Relevance of Age-Related Immune DysfunctionClinical Infectious Diseases, 2000