Elderly dendritic cells respond to LPS/IFN-gamma and CD40L stimulation despite incomplete maturation

Joanne K. Gardner, Scott M. J. Cornwall, Arthur W. Musk, John Alvarez, Cyril D. S. Mamotte, Connie Jackaman, Anna K. Nowak, Delia J. Nelson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number0195313
Number of pages23
JournalPLoS One
Volume13
Issue number4
DOIs
Publication statusPublished - 13 Apr 2018

Cite this

Gardner, J. K., Cornwall, S. M. J., Musk, A. W., Alvarez, J., Mamotte, C. D. S., Jackaman, C., ... Nelson, D. J. (2018). Elderly dendritic cells respond to LPS/IFN-gamma and CD40L stimulation despite incomplete maturation. PLoS One, 13(4), [0195313]. https://doi.org/10.1371/journal.pone.0195313