Cigarette smoke alters the ability of human dendritic cells to promote anti-Streptococcus pneumoniae Th17 response - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Respiratory Research Année : 2015

Cigarette smoke alters the ability of human dendritic cells to promote anti-Streptococcus pneumoniae Th17 response

Nicolas Just
  • Fonction : Auteur
  • PersonId : 986769

Résumé

AbstractBackgroundChronic 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.MethodsPro-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.ResultsPBMC 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.ConclusionsWe 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.
Fichier principal
Vignette du fichier
12931_2016_Article_408.pdf (1.32 Mo) Télécharger le fichier
12931_2016_408_MOESM2_ESM.pdf (29.06 Ko) Télécharger le fichier
12931_2016_408_MOESM3_ESM.pdf (46.99 Ko) Télécharger le fichier
12931_2016_408_MOESM4_ESM.pdf (44.94 Ko) Télécharger le fichier
12931_2016_408_MOESM5_ESM.pdf (422.63 Ko) Télécharger le fichier
12931_2016_408_MOESM6_ESM.pdf (39.59 Ko) Télécharger le fichier
12931_2016_408_MOESM7_ESM.pdf (50.85 Ko) Télécharger le fichier
Origine : Publication financée par une institution
Origine : Publication financée par une institution
Origine : Publication financée par une institution
Origine : Publication financée par une institution
Origine : Publication financée par une institution
Origine : Publication financée par une institution
Origine : Publication financée par une institution

Dates et versions

inserm-01349118 , version 1 (26-07-2016)

Identifiants

Citer

Olivier Le Rouzic, Bachirou Koné, Jerome Kluza, Philippe Marchetti, Florence Hennegrave, et al.. Cigarette smoke alters the ability of human dendritic cells to promote anti-Streptococcus pneumoniae Th17 response. Respiratory Research, 2015, 17 (1), pp.94. ⟨10.1186/s12931-016-0408-6⟩. ⟨inserm-01349118⟩
97 Consultations
703 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More