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dc.contributor.authorGardner, J.
dc.contributor.authorCornwall, S.
dc.contributor.authorMusk, A.
dc.contributor.authorAlvarez, J.
dc.contributor.authorMamotte, Cyril
dc.contributor.authorJackaman, Connie
dc.contributor.authorNowak, A.
dc.contributor.authorNelson, Delia
dc.identifier.citationGardner, J. and Cornwall, S. and Musk, A. and Alvarez, J. and Mamotte, C. and Jackaman, C. and Nowak, A. et al. 2018. Elderly dendritic cells respond to LPS/IFN-γ and CD40L stimulation despite incomplete maturation. PLoS ONE. 13 (4): Article ID e0195313.

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)-γ 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-γ 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-γ, tumour necrosis factor (TNF)-α, IL-6 and/or IL-12), and/or secreted cytokine levels (IFN-α, IFN-γ, TNF-α, and IL-12) to their younger counterparts. Furthermore, elderly-derived LPS/IFN-γ 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-γ-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-γ 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.

dc.publisherPublic Library of Science
dc.titleElderly dendritic cells respond to LPS/IFN-γ and CD40L stimulation despite incomplete maturation
dc.typeJournal Article
dcterms.source.titlePLoS ONE
curtin.departmentSchool of Pharmacy and Biomedical Sciences
curtin.accessStatusOpen access

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