Suppression of phosphoinositide 3-kinase signaling by cigarette smoke attenuates release of IFN-A by human plasmacytoid dendritic cells

Myeloid and plasmacytoid dendritic cells (mDCs, pDC) are crucial immune cells detecting microorganisms and linking innate and adaptive immunity. mDC are antigen presenting cells and pDC are intermediate cells. They produce large amounts of IFN-a after stimulation with CpG motifs and are also antigen presenting cells. The antiviral effect exerted by IFN-a is due to the induction of IFN response genes. Chronic airway inflammation is a cardinal feature of chronic obstructive pulmonary disease (COPD), a destructive cigarette smoke-induced lung disease. COPD patients are more susceptible to viral infections. Previously, we have demonstrated that exposure of mDC to cigarette smoke extract (CSE) lead to release of chemokines from these cells. Not much is known about the number and role of pDC in smokers with COPD. In this study, we addressed several key questions with respect to the mechanismof action of CSE on human pDC in an in vitromodel. Human pDCs were isolated from normal healthy volunteers and subjected to fresh CSE. The release of protein and expression of mRNA of IFN-a were studied by ELISA and real time PCR methods, respectively. We observed that CSE suppressed release of IFN-a. Moreover, CSE suppressed PI3K/Akt signalling in pDC. Thus, our data indicate that cigarette smoke by suppression of releases of IFN-a production may play role in diminishing anti-viral immunity.