Impaired functions of peripheral blood monocyte subpopulations in aged humans

Nyugen, Joseph; Agrawal, Sudhanshu; Gollapudi, Sastry; Gupta, Sudhir

doi:10.1007/s10875-010-9448-8

Cited by 254Immune Response and InflammationImmune cells in cancerImmune responses and vaccinations

Impaired functions of peripheral blood monocyte subpopulations in aged humans

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Nyugen, Joseph, Agrawal, Sudhanshu, Gollapudi, Sastry, Gupta, Sudhir·2010·Journal of Clinical Immunology

DOI 10.1007/s10875-010-9448-8PMC PMC2970801

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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 CD14(high) or CD14(+low), therefore highlighting the significance of further subdivision of monocytes into four subpopulations.

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When stimulated with TLR1/2 agonists such as PamCy3, monocytes from older people produce less TNFα and IL-6 than monocytes from young people.
“When monocytes are stimulated with TLR1/2 stimuli such as PamCy3 there reduced production of TNFα and IL-6 from aged monocytes as compared to young”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [129]
The lower TLR1/2-stimulated cytokine production in aged monocytes is thought to result from decreased TLR1 expression on monocytes of older individuals.
“this is believed to be due to a reduced expression of TLR1 on the monocytes of older individuals (129, 135).”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [129]

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[26]Agarwal A Agrawal S Cao JN Su H Osann K GUPTA S Abberant innate functions of dendritic cells in aged humans: a role of PI3-K signaling pathway J Immunol 2007 178 6912 6922 17513740

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Authors: Nyugen, J., Agrawal, S., Gollapudi, S., & Gupta, S.
Affiliations: University of California, Irvine (US)
Corresponding author: Gupta, Sudhir
ORCID: Gupta, Sudhir
Venue: Journal of Clinical Immunology
Publisher: Springer Science and Business Media LLC
Published: 2010-08-12
Volume: 30
Issue: 6
Pages: 806-813
ISSN: 0271-9142 (ISSN-L)
1573-2592
DOI: 10.1007/s10875-010-9448-8
PMC: PMC2970801
OpenAlex: W2015163231
Cited by: 249
References: 31
Citations by year: 2026: 6 · 2025: 22 · 2024: 19 · 2023: 17 · 2022: 13 · 2021: 32 · 2020: 18 · 2019: 13 · 2018: 12 · 2017: 15 · 2016: 11 · 2015: 12 · 2014: 19 · 2013: 20 · 2012: 13
FWCI: 5.09
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: Journal of Clinical Immunology (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
eScholarship (California Digital Library) (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords: monocyte subpopulations, aging, CD14, CD16, TLR1, ERK1/2 phosphorylation, MAPK signaling, interleukin-6, TNF-α, cytokine production, Pam3Cys, immunosenescence
MeSH terms: Adult, Aged, Aged, 80 and over, Aging, Bacterial Infections, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Humans, Macrophages, Signal Transduction, Antigens, CD, Interleukin-6, Mitogen-Activated Protein Kinase 3, Toll-Like Receptors

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Impaired functions of peripheral blood monocyte subpopulations in aged humans

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