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Quantitative Imaging of Lineage-specific Toll-like Receptor-mediated Signaling in Monocytes and Dendritic Cells from Small Samples of Human Blood
Published on: April 16, 2012
Impaired functions of peripheral blood monocyte subpopulations in aged humans
Joseph Nyugen1, Sudhanshu Agrawal, Sastry Gollapudi
1Division of Basic and Clinical Immunology, University of California, Med. Sci I, C-240, Irvine, CA 92697, USA.
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.
Insights
Aging impairs monocyte function, decreasing cytokine production and Toll-like receptor (TLR) expression. These changes, particularly in CD16+ monocytes, affect microbial defense in older adults.
Area of Science:
- Immunology
- Gerontology
- Cell Biology
Background:
- Aging increases susceptibility to infections.
- Monocytes are crucial for microbial defense.
- Specific monocyte subpopulations and their age-related changes are not fully understood.
Purpose of the Study:
- To compare four monocyte subpopulations in young and aged individuals.
- To analyze numbers, cytokine production, Toll-like receptor (TLR) expression, and ERK1/2 phosphorylation.
- To investigate the functional impact of aging on monocyte subsets.
Main Methods:
- Flow cytometry was used to identify and quantify four monocyte subsets (CD14(++(high))CD16(-), CD14(+(low))CD16(-), CD14(++(high))CD16(+), and CD14(+(low))CD16(+)).
- Cytokine production (IL-6, TNF-α), TLR1 expression, and ERK1/2 phosphorylation after pam3Cys stimulation were measured.
- Comparisons were made between young and aged subjects.
Main Results:
- Aged subjects showed increased CD14(++(high))CD16(+) and CD14(+(low))CD16(+) monocytes, and decreased CD14(+(low))CD16(-) monocytes.
- Aged monocytes exhibited reduced IL-6 and TNF-α production.
- Decreased TLR1 expression and impaired ERK1/2 phosphorylation were observed in aged monocyte subsets, especially CD16+ cells.
Conclusions:
- Aging differentially impairs the function of monocyte subpopulations.
- CD16+ monocyte subsets show significant functional deficits in aging.
- Understanding these age-related monocyte changes is crucial for improving immune defense in the elderly.
