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

• Published in: PloS one Vol. 13; no. 4; p. e0195313
• Main Authors: Gardner, Joanne K, Cornwall, Scott M J, Musk, Arthur W, Alvarez, John, Mamotte, Cyril D S, Jackaman, Connie, Nowak, Anna K, Nelson, Delia J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-04-2018; Public Library of Science (PLoS)
• Subjects: Adenosine; Age; Aging; Anticancer properties; Antigen processing; Antigen-presenting cells; Antigens; Apoptosis; Biology and Life Sciences; CD4 antigen; CD40 antigen; CD40L protein; CD8 antigen; CD80 antigen; CD86 antigen; Cell proliferation; Cytokines; Cytotoxicity; Dendritic cells; Effector cells; Geriatrics; Hazards; Hospitals; Immune response; Immunology; Infections; Inflammation; Inflammatory response; Interferon; Interleukin 12; Interleukin 6; Interleukin 8; Ligands; Lipopolysaccharides; Lymphocytes; Lymphocytes T; Maturation; Medicine and Health Sciences; Monocyte chemoattractant protein; Monocytes; Older people; Ovalbumin; People and Places; Pharmacy; Priming; Research and Analysis Methods; Rodents; Stimulation; T cell receptors; TNF inhibitors; Tumor necrosis factor-TNF; Tumors; α-Interferon; γ-Interferon; Australia; Western Australia Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0195313

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 pro-inflammatory 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.