TY - JOUR
T1 - Elderly dendritic cells respond to LPS/IFN-gamma and CD40L stimulation despite incomplete maturation
AU - Gardner, Joanne K.
AU - Cornwall, Scott M. J.
AU - Musk, Arthur W.
AU - Alvarez, John
AU - Mamotte, Cyril D. S.
AU - Jackaman, Connie
AU - Nowak, Anna K.
AU - Nelson, Delia J.
PY - 2018/4/13
Y1 - 2018/4/13
N2 - There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However, the effects of aging on DC responses to bacterial lipopolysaccharide (LPS), the proinflammatory cytokine interferon (IFN)-gamma and CD40 ligand (CD40L) have not yet been systematically evaluated. We examined responses of blood myeloid (m) DC1s, mDC2s, plasmacytoid (p) DCs, and monocyte-derived DCs (MoDCs) from young (21 +/- 40 years) and elderly (60 +/- 84 years) healthy human volunteers to LPS/IFN-gamma or CD40L stimulation. All elderly DC subsets demonstrated comparable up-regulation of co-stimulatory molecules (CD40, CD80 and/or CD86), intracellular pro-inflammatory cytokine levels (IFN-gamma, tumour necrosis factor (TNF)-alpha, IL-6 and/or IL-12), and/or secreted cytokine levels (IFN-alpha, IFN-gamma, TNF-alpha, and IL-12) to their younger counterparts. Furthermore, elderly-derived LPS/IFN-gamma or CD40L-activated MoDCs induced similar or increased levels of CD8(+) and CD4(+) T cell proliferation, and similar T cell functional phenotypes, to their younger counterparts. However, elderly LPS/IFN-gamma-activated MoDCs were unreliable in their ability to up-regulate chemokine (IL-8 and monocyte chemoattractant protein (MCP)-1) and IL-6 secretion, implying an inability to dependably induce an inflammatory response. A key age-related difference was that, unlike young-derived MoDCs that completely lost their ability to process antigen, elderly-derived MoDCs maintained their antigen processing ability after LPS/IFN-gamma maturation, measured using the DQ-ovalbumin assay; this response implies incomplete maturation that may enable elderly DCs to continuously present antigen. These differences may impact on the efficacy of anti-pathogen and anti-tumour immune responses in the elderly.
AB - There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However, the effects of aging on DC responses to bacterial lipopolysaccharide (LPS), the proinflammatory cytokine interferon (IFN)-gamma and CD40 ligand (CD40L) have not yet been systematically evaluated. We examined responses of blood myeloid (m) DC1s, mDC2s, plasmacytoid (p) DCs, and monocyte-derived DCs (MoDCs) from young (21 +/- 40 years) and elderly (60 +/- 84 years) healthy human volunteers to LPS/IFN-gamma or CD40L stimulation. All elderly DC subsets demonstrated comparable up-regulation of co-stimulatory molecules (CD40, CD80 and/or CD86), intracellular pro-inflammatory cytokine levels (IFN-gamma, tumour necrosis factor (TNF)-alpha, IL-6 and/or IL-12), and/or secreted cytokine levels (IFN-alpha, IFN-gamma, TNF-alpha, and IL-12) to their younger counterparts. Furthermore, elderly-derived LPS/IFN-gamma or CD40L-activated MoDCs induced similar or increased levels of CD8(+) and CD4(+) T cell proliferation, and similar T cell functional phenotypes, to their younger counterparts. However, elderly LPS/IFN-gamma-activated MoDCs were unreliable in their ability to up-regulate chemokine (IL-8 and monocyte chemoattractant protein (MCP)-1) and IL-6 secretion, implying an inability to dependably induce an inflammatory response. A key age-related difference was that, unlike young-derived MoDCs that completely lost their ability to process antigen, elderly-derived MoDCs maintained their antigen processing ability after LPS/IFN-gamma maturation, measured using the DQ-ovalbumin assay; this response implies incomplete maturation that may enable elderly DCs to continuously present antigen. These differences may impact on the efficacy of anti-pathogen and anti-tumour immune responses in the elderly.
KW - IMMUNE REGULATION
KW - INTERFERON-GAMMA
KW - AGED MICE
KW - T-CELLS
KW - SECRETION
KW - INNATE
KW - CANCER
KW - DIFFERENTIATION
KW - INFLAMMATION
KW - MACROPHAGES
U2 - 10.1371/journal.pone.0195313
DO - 10.1371/journal.pone.0195313
M3 - Article
SN - 1932-6203
VL - 13
JO - PLoS One
JF - PLoS One
IS - 4
M1 - e0195313
ER -
