title: IL-22 Defect During Streptococcus pneumoniae Infection Triggers Exacerbation of Chronic Obstructive Pulmonary Disease.
abstract: Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation.
authors: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France; Université Lille Nord de France, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59021 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59019 Lille, France; Institut Fédératif de Recherche 142, F-59019 Lille, France.
authors: Muriel
authors: M
authors: Pichavant
authors: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France; Université Lille Nord de France, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59021 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59019 Lille, France; Institut Fédératif de Recherche 142, F-59019 Lille, France.
authors: Riti
authors: R
authors: Sharan
authors: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France; Université Lille Nord de France, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59021 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59019 Lille, France; Institut Fédératif de Recherche 142, F-59019 Lille, France; Service de Pneumologie, Hôpital Calmette, CHRU, Lille, France.
authors: Olivier
authors: O
authors: Le Rouzic
authors: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France; Université Lille Nord de France, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59021 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59019 Lille, France; Institut Fédératif de Recherche 142, F-59019 Lille, France; Service de Pneumologie, Hôpital Calmette, CHRU, Lille, France.
authors: Cécile
authors: C
authors: Olivier
authors: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France; Université Lille Nord de France, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59021 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59019 Lille, France; Institut Fédératif de Recherche 142, F-59019 Lille, France; Service de Pneumologie, Hôpital Calmette, CHRU, Lille, France.
authors: Florence
authors: F
authors: Hennegrave
authors: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France; Université Lille Nord de France, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59021 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59019 Lille, France; Institut Fédératif de Recherche 142, F-59019 Lille, France.
authors: Gaëlle
authors: G
authors: Rémy
authors: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France; Université Lille Nord de France, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59021 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59019 Lille, France; Institut Fédératif de Recherche 142, F-59019 Lille, France.
authors: Magdiel
authors: M
authors: Pérez-Cruz
authors: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France; Université Lille Nord de France, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59021 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59019 Lille, France; Institut Fédératif de Recherche 142, F-59019 Lille, France.
authors: Bachirou
authors: B
authors: Koné
authors: Service d'Anatomo-Pathologie, Hôpital Saint Vincent de Paul, Lille, France.
authors: Pierre
authors: P
authors: Gosset
authors: Service de Pneumologie, Hôpital Victor Provo, Roubaix, France.
authors: Nicolas
authors: N
authors: Just
authors: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France; Université Lille Nord de France, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59021 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59019 Lille, France; Institut Fédératif de Recherche 142, F-59019 Lille, France.
authors: Philippe
authors: P
authors: Gosset
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D007378:Interleukins / Q000172:deficiency*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000150:complications* / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22
keywords: AM, alveolar macrophages; APC, antigen presenting cells; BAL, broncho-alveolar lavage; Bacterial infection; CFU, colony forming unit; COPD, chronic obstructive pulmonary disease; CS, cigarette smoke; Chronic obstructive pulmonary disease; DC, dendritic cells; IL-22; Innate immunity; NK, natural killer cells; NKT, natural killer T cells; PBMC, peripheral blood mononuclear cells; Sp, Streptococcus pneumoniae