title: Interleukin-22 protects against non-typeable Haemophilus influenzae infection: alteration during chronic obstructive pulmonary disease.
abstract: Chronic obstructive pulmonary disease is a major health problem becoming a leading cause of morbidity and mortality worldwide. A large part of these disorders is associated with acute exacerbations resulting from infection by bacteria, such as non-typeable Haemophilus influenzae (NTHi). Our understanding of the pathogenesis of these exacerbations is still elusive. We demonstrate herein that NTHi infection of mice chronically exposed to cigarette smoke (CS), an experimental model of chronic obstructive pulmonary disease (COPD), not only causes acute pulmonary inflammation but also impairs the production of interleukin (IL)-22, a cytokine with potential anti-bacterial activities. We also report that mice lacking IL-22, as well as mice exposed to CS, have a delayed clearance of NTHi bacteria and display enhanced alveolar wall thickening and airway remodeling compared with controls. Supplementation with IL-22 not only boosted bacterial clearance and the production of anti-microbial peptides but also limited lung damages induced by infection both in IL-22-/-and CS-exposed mice. In vitro exposure to CS extract altered the NTHi-induced IL-22 production by spleen cells. This study shows for the first time that a defect in IL-22 is involved in the acute exacerbation induced by NTHi infection during experimental COPD and opens the way to innovative therapeutic strategies.
authors.affiliation: Université Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: R
authors.initials: R
authors.lastname: Sharan
authors.affiliation: Université Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Perez-Cruz
authors.affiliation: Université Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: G
authors.initials: G
authors.lastname: Kervoaze
authors.affiliation: Service d'Anatomo-pathologie, Hôpital Saint Vincent de Paul, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Weynants
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Godfroid
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Hermand
authors.affiliation: Université Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Trottein
authors.affiliation: Université Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Pichavant
authors.affiliation: Université Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: P
authors.initials: P
authors.lastname: Gosset
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D058491:Bacterial Load; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006192:Haemophilus Infections / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000382:microbiology; D012907:Smoking / Q000009:adverse effects; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D000097043:Interleukin-22