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

Brodie Miles,Ahmed Y Gamal,Khaled A Abdel-Ghaffar,Babak Baban,Christopher W Cutler

doi:10.3389/fmicb.2014.00006

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.

Highlights

TO BLOOD DENDRITIC CELLS Tissue dendritic cells (DCs) are the peripheral sentinels of the human immune system (Banchereau and Steinman, 1998)
The major response of CD141(+) myeloid DCs (mDCs) to Toll-like receptor (TLR)-3 ligand and their cytokine production pattern suggest a role for these cells in antiviral immunity (Hemont et al, 2013)
Peripheral blood mDCs are differentially regulated by the cytokine milieu, which leads to alterations in surface expression of major histocompatibility complex class II (MHC-II) and accessory molecules (Kohrgruber et al, 1999)

Summary

INTRODUCTION

TO BLOOD DENDRITIC CELLS Tissue dendritic cells (DCs) are the peripheral sentinels of the human immune system (Banchereau and Steinman, 1998). MoDCs (León et al, 2005) have been used to study the role of various stress conditions such as graft vs host rejection (Antonysamy et al, 1999; Lutz et al, 2000), TLR stimulation (Krutzik et al, 2005), and autoimmunity (Blanco et al, 2001) and cancer (Thurner et al, 1999; Kiertscher et al, 2000; Schuler-Thurner et al, 2002; Figdor et al, 2004) Myeloid precursors such as monocytes can rapidly differentiate into distinct populations of mDCs not typically present during steady state conditions, when encountering microbial and inflammatory signals. Peripheral blood mDCs are differentially regulated by the cytokine milieu, which leads to alterations in surface expression of major histocompatibility complex class II (MHC-II) and accessory molecules (Kohrgruber et al, 1999) These circulating cells appear capable of processing antigen and stimulating adaptive immunity, but this can be manipulated by their environment (Thomas and Lipsky, 1994; Ito et al, 2001).

Asthma and allergies

Findings

Increased blood mDCs