title: Cigarette smoke alters the ability of human dendritic cells to promote anti-Streptococcus pneumoniae Th17 response.
abstract: Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation and impaired immune response to pathogens leading to bacteria-induced exacerbation of the disease. A defect in Th17 cytokines in response to Streptococcus pneumoniae, a bacteria associated with COPD exacerbations, has been recently reported. Dendritic cells (DC) are professional antigen presenting cells that drive T-cells differentiation and activation. In this study, we hypothesized that exposure to cigarette smoke, the main risk factor of COPD, might altered the pro-Th17 response to S. pneumoniae in COPD patients and human DC.
  
  
  
  Pro-Th1 and -Th17 cytokine production by peripheral blood mononuclear cells (PBMC) from COPD patients was analyzed and compared to those from smokers and non-smokers healthy subjects. The effect of cigarette smoke extract (CSE) was analyzed on human monocyte-derived DC (MDDC) from controls exposed or not to S. pneumoniae. Bacteria endocytosis, maturation of MDDC and secretion of cytokines were assessed by flow cytometry and ELISA, respectively. Implication of the oxidative stress was analyzed by addition of antioxidants and mitochondria inhibitors. In parallel, MDDC were cocultured with autologous T-cells to analyze the consequence on Th1 and Th17 cytokine production.
  
  
  
  PBMC from COPD patients exhibited defective production of IL-1β, IL-6, IL-12 and IL-23 to S. pneumoniae compared to healthy subjects and smokers. CSE significantly reduced S. pneumoniae-induced MDDC maturation, secretion of pro-Th1 and -Th17 cytokines and activation of Th1 and Th17 T-cell responses. CSE exposure was also associated with sustained CXCL8 secretion, bacteria endocytosis and mitochondrial oxidative stress. Antioxidants did not reverse these effects. Inhibitors of mitochondrial electron transport chain partly reproduced inhibition of S. pneumoniae-induced MDDC maturation but had no effect on cytokine secretion and T cell activation.
  
  
  
  We observed a defective pro-Th1 and -Th17 response to bacteria in COPD patients. CSE exposure was associated with an inhibition of DC capacity to activate antigen specific T-cell response, an effect that seems to be not only related to oxidative stress. These results suggest that new therapeutics boosting this response in DC may be helpful to improve treatment of COPD exacerbations.
authors.affiliation: Univ. Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France.|CNRS, UMR 8204, F-59000, Lille, France.|Inserm, U1019, F-59000, Lille, France.|CHU Lille, Service de Pneumologie Immunologie et Allergologie, F-59000, Lille, France.|Institut Pasteur de Lille, F-59000, Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Le Rouzic
authors.affiliation: Univ. Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France.|CNRS, UMR 8204, F-59000, Lille, France.|Inserm, U1019, F-59000, Lille, France.|Institut Pasteur de Lille, F-59000, Lille, France.
authors.forename: Bachirou
authors.initials: B
authors.lastname: Koné
authors.affiliation: Univ. Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000, Lille, France.|Inserm, UMR-S 1172, F-59000, Lille, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Kluza
authors.affiliation: Univ. Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000, Lille, France.|Inserm, UMR-S 1172, F-59000, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: CHU Lille, Service de Pneumologie Immunologie et Allergologie, F-59000, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Hennegrave
authors.affiliation: CHU Lille, Service de Pneumologie Immunologie et Allergologie, F-59000, Lille, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Olivier
authors.affiliation: Univ. Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France.|CNRS, UMR 8204, F-59000, Lille, France.|Inserm, U1019, F-59000, Lille, France.|Institut Pasteur de Lille, F-59000, Lille, France.
authors.forename: Gwenola
authors.initials: G
authors.lastname: Kervoaze
authors.affiliation: Univ. Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France.|CNRS, UMR 8204, F-59000, Lille, France.|Inserm, U1019, F-59000, Lille, France.|Institut Pasteur de Lille, F-59000, Lille, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Vilain
authors.affiliation: Univ. Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France.|CNRS, UMR 8204, F-59000, Lille, France.|Inserm, U1019, F-59000, Lille, France.|Institut Pasteur de Lille, F-59000, Lille, France.|CHU Lille, Service de Pédiatrie, F-59000, Lille, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Mordacq
authors.affiliation: CH Roubaix, Service de Pneumologie, F-59100, Roubaix, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Just
authors.affiliation: CHU Lille, Service de Pneumologie Immunologie et Allergologie, F-59000, Lille, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Perez
authors.affiliation: CHU Lille, Service de Pneumologie Immunologie et Allergologie, F-59000, Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bautin
authors.affiliation: Univ. Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France.|CNRS, UMR 8204, F-59000, Lille, France.|Inserm, U1019, F-59000, Lille, France.|Institut Pasteur de Lille, F-59000, Lille, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Pichavant
authors.affiliation: Univ. Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France. philippe.gosset@pasteur-lille.fr.|CNRS, UMR 8204, F-59000, Lille, France. philippe.gosset@pasteur-lille.fr.|Inserm, U1019, F-59000, Lille, France. philippe.gosset@pasteur-lille.fr.|Institut Pasteur de Lille, F-59000, Lille, France. philippe.gosset@pasteur-lille.fr.|LI3, CIIL - Institut Pasteur de Lille, F-59000, Lille, France. philippe.gosset@pasteur-lille.fr.
authors.forename: Philippe
authors.identifier: 0000-0002-4043-6429
authors.initials: P
authors.lastname: Gosset
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D001770:Blood Bactericidal Activity; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism; D012906:Smoke; D012907:Smoking / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D014026:Nicotiana / Q000633:toxicity
chemical_list: D000975:Antioxidants; D016207:Cytokines; D012906:Smoke
keywords: Chronic obstructive pulmonary disease; Dendritic cells; Interleukin-1β; Interleukin-23; Smoking; Streptococcus pneumoniae; Th17 cytokines