Blood dendritic cells: “canary in the coal mine” to predict chronic inflammatory disease?

Abstract

The majority of risk factors for chronic inflammatory diseases are unknown. This makes personalized medicine for assessment, prognosis, and choice of therapy very difficult. It is becoming increasingly clear, however, that low-grade subclinical infections may be an underlying cause of many chronic inflammatory diseases and thus may contribute to secondary outcomes (e.g., cancer). Many diseases are now categorized as inflammatory-mediated diseases that stem from a dysregulation in host immunity. There is a growing need to study the links between low-grade infections, the immune responses they elicit, and how this impacts overall health. One such link explored in detail here is the extreme sensitivity of myeloid dendritic cells (mDCs) in peripheral blood to chronic low-grade infections and the role that these mDCs play in arbitrating the resulting immune responses. We find that emerging evidence supports a role for pathogen-induced mDCs in chronic inflammation leading to increased risk of secondary clinical disease. The mDCs that are elevated in the blood as a result of low-grade bacteremia often do not trigger a productive immune response, but can disseminate the pathogen throughout the host. This aberrant trafficking of mDCs can accelerate systemic inflammatory disease progression. Conversely, restoration of dendritic cell homeostasis may aid in pathogen elimination and minimize dissemination. Thus it would seem prudent when assessing chronic inflammatory disease risk to consider blood mDC numbers, and the microbial content (microbiome) and activation state of these mDCs. These may provide important clues (“the canary in the coal mine”) of high inflammatory disease risk. This will facilitate development of novel immunotherapies to eliminate such smoldering infections in atherosclerosis, cancer, rheumatoid arthritis, and pre-eclampsia.

Ginsenoside Metabolite Compound K Suppresses T-Cell Priming via Modulation of Dendritic Cell Trafficking and Costimulatory Signals, Resulting in Alleviation of Collagen-Induced Arthritis

“…DCs have been shown to continuously present endogenous antigens and prime the T-cell response in inflammatory conditions (Leung et al, 2002;Eriksson et al, 2003;Bailey et al, 2007). The role of DCs in the pathogenesis of autoimmune disease, such as RA, has been confirmed in numerous studies (Pulendran et al, 2010;Rodríguez-Fernández, 2013;Miles et al, 2014). Studies have demonstrated that the infiltrated DCs in the inflamed synovial tissue subsequently migrate to the draining lymph nodes and present arthritogenic peptide to T cells and induce naive T-cell activation (Pettit et al, 2000;Lutzky et al, 2007).…”

Dendritic cells matured in the presence of the lycopodium alkaloid annotine direct T cell responses toward a Th2/Treg phenotype

“…annotine. As DCs are the most potent professional antigen-presenting cells and can have a major effects on T cell responses they are attractive targets for clinical therapies targeting autoimmune diseases and chronic infections (Miles et al 2014). We, therefore, used DCs and co-cultures of DCs and T cells to study the potential of annotine to affect DC activation and how annotine-treated DCs modulate T cell responses.…”

Ginsenoside metabolite compound K exerts anti-inflammatory effect via suppressing T cell activation

“…DCs present antigens to T cells and induce T cell activation in inflammatory conditions [21][22][23] . It has been reported in numerous studies that DCs play important role in the pathogenesis of autoimmune disease such as RA [24][25][26] . The infiltrated DCs migrate from the inflamed synovium to the draining lymph nodes, present arthritogenic peptide to T cells and activate T cells [27,28] .…”