TY - JOUR T1 - Exposure to cigarette smoke affects the response of dendritic cells to pneumococcus JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p3871 AU - Olivier Le Rouzic AU - Gaëlle Remy AU - Cyrielle Jardin AU - Isabelle Tillie-Leblond AU - Muriel Pichavant AU - Philippe Gosset Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p3871.abstract N2 - Development of chronic obstructive pulmonary disease (COPD) is linked to tabagism. Acute exacerbation potentially related to infection by streptococcus pneumoniae is responsible for the progression of the disease. Innate immunity associated with dendritic cells (DC) mobilization is involved in the pathophysiology of the disease. We hypothesize that cigarette smoke impairs the response of DC to pathogens, a mechanism that may be involved in COPD progression.Monocyte-derived DC of healthy donors were exposed to cigarette smoke extract (CSE) and next to pneumococcus (serotype 1). First, endocytosis and bactericidy of S. pneumoniae was analyzed. DC phenotype (costimulatory molecules and endocytosis receptors) and production of immunoregulatory cytokines was measured as well as the capacity of DC to activate autologous T-cells.Our data showed that CSE exposure inhibited the pneumococcus-dependent expression of CD40, CD80 and CD86 costimulatory molecules. Similarly, proinflammatory cytokine production (IL-12 and TNF-α) was inhibited by CSE exposure. In DC/T coculture, this was associated with a decrease secretion of IL-17 and IFN-γ by T cells. Unexpectedly, this exposure to CSE increased the endocytosis of pneumococcus, whereas CD206 and CD36 expression was affected in an opposite manner. The effect of CSE was mostly related to oxidative stress since it was inhibited by addition of N-acetyl cystein.In summary, CSE exposure impairs the capacity of DC to activate antigen-specific T-cells against pneumococcus, although it does not alter their endocytosis. These data will be conforted by the ex vivo analysis of DC phenotype in COPD patients with exacerbation. ER -