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Alterations to the frequency and function of peripheral blood monocytes and associations with chronic disease in the advanced-age, frail elderly.

Verschoor CP, Johnstone J, Millar J, Parsons R, Lelic A, Loeb M, Bramson JL, Bowdish DM - PLoS ONE (2014)

Bottom Line: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs).Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.Whether these changes contribute to or are caused by these conditions warrants further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT

Background: Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.

Design: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.

Results: The advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.

Conclusions: These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.

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Related in: MedlinePlus

Summary of the gating strategy to define blood monocyte (upper panel) and dendritic cell (lower panel) subsets.Monocytes were defined as CD45 and HLA-DR expressing and lineage (CD2, CD3, CD15, CD19, CD56, NKp46) negative. Dendritic cell subsets were defined as CD45 and HLA-DR expressing, lineage (CD3, CD15, CD19, CD56) negative, and CD123 bright plasmacytoid dendritic cells (pDCs) or CD123 low, and CD1c or CD141 expressing myeloid dendritic cells (mDCs).
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pone-0104522-g001: Summary of the gating strategy to define blood monocyte (upper panel) and dendritic cell (lower panel) subsets.Monocytes were defined as CD45 and HLA-DR expressing and lineage (CD2, CD3, CD15, CD19, CD56, NKp46) negative. Dendritic cell subsets were defined as CD45 and HLA-DR expressing, lineage (CD3, CD15, CD19, CD56) negative, and CD123 bright plasmacytoid dendritic cells (pDCs) or CD123 low, and CD1c or CD141 expressing myeloid dendritic cells (mDCs).

Mentions: Antibody staining was performed as described previously [14]. For the comparison of young adults, community-dwelling seniors and advanced-age, frail elderly, fluorochrome conjugated antibodies included: CD2-PE, CD3-PE, CD16-PE, CD19-PE, CD56-PE, NKp46-PE, CCR2-Alexa647 (BD Biosciences, NJ, USA); CD15-PE, CD1c-FITC, CD141-APC (Miltenyi Biotec, CA, USA); CD14-APC-Alexa750 (Invitrogen, ON, CAN); CX3CR1-FITC (Biolegend, CA, USA); CD16-PE-Cy7, HLADR-PerCp-Cy5.5, CD45-eFluor605NC, CD123-PE-Cy7, TLR-4-Alexa700, TLR-2-eFluor450 (eBioscience, CA, USA). For monocyte staining, lineage cells were defined as CD2, CD3, CD15, CD19, CD56 and NKp46 positive, and CD16 thresholds were defined using a fluorescent-minus-one (FMO) with isotype control (Figure 1). For DC staining, lineage cells were defined as CD3, CD15, CD16, CD19 and CD56 positive (Figure 1). Thresholds to determine percentage of cells expressing CCR2, CX3CR1, TLR-2 and TLR-4 were calculated using an FMO with isotype control or negative staining population where appropriate. The frequency of monocyte and DC subsets is presented as per µl of whole blood (calculated using CountBright absolute counting beads) as well as the percentage of CD45 expressing PBMCs. Proportions of monocyte and DC subsets were defined as the percentage of CD45 expressing PBMCs. All analyses were performed in FlowJo 7.6.4 (Treestar, OR, USA).


Alterations to the frequency and function of peripheral blood monocytes and associations with chronic disease in the advanced-age, frail elderly.

Verschoor CP, Johnstone J, Millar J, Parsons R, Lelic A, Loeb M, Bramson JL, Bowdish DM - PLoS ONE (2014)

Summary of the gating strategy to define blood monocyte (upper panel) and dendritic cell (lower panel) subsets.Monocytes were defined as CD45 and HLA-DR expressing and lineage (CD2, CD3, CD15, CD19, CD56, NKp46) negative. Dendritic cell subsets were defined as CD45 and HLA-DR expressing, lineage (CD3, CD15, CD19, CD56) negative, and CD123 bright plasmacytoid dendritic cells (pDCs) or CD123 low, and CD1c or CD141 expressing myeloid dendritic cells (mDCs).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126708&req=5

pone-0104522-g001: Summary of the gating strategy to define blood monocyte (upper panel) and dendritic cell (lower panel) subsets.Monocytes were defined as CD45 and HLA-DR expressing and lineage (CD2, CD3, CD15, CD19, CD56, NKp46) negative. Dendritic cell subsets were defined as CD45 and HLA-DR expressing, lineage (CD3, CD15, CD19, CD56) negative, and CD123 bright plasmacytoid dendritic cells (pDCs) or CD123 low, and CD1c or CD141 expressing myeloid dendritic cells (mDCs).
Mentions: Antibody staining was performed as described previously [14]. For the comparison of young adults, community-dwelling seniors and advanced-age, frail elderly, fluorochrome conjugated antibodies included: CD2-PE, CD3-PE, CD16-PE, CD19-PE, CD56-PE, NKp46-PE, CCR2-Alexa647 (BD Biosciences, NJ, USA); CD15-PE, CD1c-FITC, CD141-APC (Miltenyi Biotec, CA, USA); CD14-APC-Alexa750 (Invitrogen, ON, CAN); CX3CR1-FITC (Biolegend, CA, USA); CD16-PE-Cy7, HLADR-PerCp-Cy5.5, CD45-eFluor605NC, CD123-PE-Cy7, TLR-4-Alexa700, TLR-2-eFluor450 (eBioscience, CA, USA). For monocyte staining, lineage cells were defined as CD2, CD3, CD15, CD19, CD56 and NKp46 positive, and CD16 thresholds were defined using a fluorescent-minus-one (FMO) with isotype control (Figure 1). For DC staining, lineage cells were defined as CD3, CD15, CD16, CD19 and CD56 positive (Figure 1). Thresholds to determine percentage of cells expressing CCR2, CX3CR1, TLR-2 and TLR-4 were calculated using an FMO with isotype control or negative staining population where appropriate. The frequency of monocyte and DC subsets is presented as per µl of whole blood (calculated using CountBright absolute counting beads) as well as the percentage of CD45 expressing PBMCs. Proportions of monocyte and DC subsets were defined as the percentage of CD45 expressing PBMCs. All analyses were performed in FlowJo 7.6.4 (Treestar, OR, USA).

Bottom Line: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs).Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.Whether these changes contribute to or are caused by these conditions warrants further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT

Background: Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.

Design: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.

Results: The advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.

Conclusions: These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.

Show MeSH
Related in: MedlinePlus