Résumés disponibles (85) :

KONÉ Bachirou (UMR8204-U1019 éq. 12 - Philippe GOSSET)
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@mail :  philippe.gosset@pasteur-lille.fr      tél. :  03 20 87 79 65

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Titre de la communication :
Cellular and molecular mechanisms of susceptibility to infection in COPD
Auteurs (et leurs adresses) de la communication :
Bachirou KONÉ, Magdiel PÉREZ-CRUZ, Fahima MADOURI, Eva VILAIN, Gwenola KERVOAZE, Muriel PICHAVANT, Philippe GOSSET Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR, 8204 - CIIL - LI3 - F-59000 Lille, France
Résumé de la communication :
Background: Chronic obstructive pulmonary disease (COPD) is a public health burden mainly due to cigarette smoke (CS) and other air pollutants. Alteration of the innate immune response to bacterial infection is a key determinant in the COPD course. It is now well recognized that respiratory infections are important triggers for the progression and exacerbation of the disease. We previously identified a defect in IL-22 as a key factor responsible for bacteria-induced exacerbations of COPD. This alteration related to deficient activation of conventional and non-conventional offers hints for the development of novel therapeutic strategies in COPD exacerbations. Our goal is to restore an appropriate immune response to pathogens during COPD. Since the IL-22 response could be regulated by cytokines such as the IL-20 family, our goal was to investigate the IL-20 pathway in order to restore an efficient response against pathogens in the lung during COPD Exacerbation.
Methods: C57BL/6 mice were daily exposed to CS during 12 weeks (COPD model) before infection by Streptococcus pneumoniae (Sp). Moreover, this bacteria was used to stimulate human monocyte-derived dendritic cells (MDDC) pre-treated or not with cigarette smoke extract (CSE). The expression of IL-20 cytokine and their receptors was evaluated. To decipher the role of the IL-20 family, the impact of blocking anti-IL-20Rb mAbs or recombinant IL-20 cytokines was evaluated on MDDC maturation. Bacterial flagellin (FliC) was systemically administrated in COPD-Sp mice to assess the potential of immunostimulants to improve bacterial clearance.
Results: We found that IL-20 cytokines are over expressed in the lung of COPD mice and were amplified after Sp challenge. Moreover, human MDDC produce IL-20 cytokines in response to CSE and/or Sp. They also express IL-20Ra, IL-20Rb and IL22Ra. IL-20 cytokines inhibited MDDC maturation in response to Sp, as shown by a decreased expression of CD86, CD80, and CD274 and a lower production of polarizing cytokines such as IL-1b, IL-6, and IL-23. As a consequence, IL-20 treated MDDC exhibited a reduced capacity to induce the production of IL-17 and IL-22 by naive T lymphocytes in response to Sp. Addition of anti-IL-20Rb mAbs boosted the production of IL-1b, IL-6, and IL-23 by MDDC, and restored the production of IL-17 and IL-22 by naive T cells. Anti-IL-20Rb mAbs reduced the inflammation and the bacterial load in the lung and bronchoalveolar lavage fluid (BALF). Finally, FliC treatment ameliorates bacterial clearance in BALF and lung, increased IL-22, neutrophils recruitment and S100A protein.
Conclusion: These results suggest that IL-20 cytokines could be involved in the susceptibility of COPD patients to infections, by targeting MDDC. Therefore, blocking anti-IL-20Rb mAbs could represent a novel therapeutic way to boost MDDC response to pathogens. Furthermore, immunostimulants such as bacterial flagellin is beneficial in COPD exacerbation mice model.

KONÉ Bachirou (UMR8204-U1019 éq. 12 - Philippe GOSSET)