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Interleukin-22 level is negatively correlated with neutrophil recruitment in the lungs in a Pseudomonas aeruginosa pneumonia model

Abstract : Pseudomonas aeruginosa is a major threat for immune-compromised patients. Bacterial pneumonia can induce uncontrolled and massive neutrophil recruitment ultimately leading to acute respiratory distress syndrome and epithelium damage. Interleukin-22 plays a central role in the protection of the epithelium. In this study, we aimed to evaluate the role of interleukin-22 and its soluble receptor IL-22BP in an acute Pseudomonas aeruginosa pneumonia model in mice. In this model, we noted a transient increase of IL-22 during Pseudomonas aeruginosa challenge. Using an antibody-based approach, we demonstrated that IL-22 neutralisation led to increased susceptibility to infection and to lung damage correlated with an increase in neutrophil accumulation in the lungs. On the contrary, rIL-22 administration or IL-22BP neutralisation led to a decrease in mouse susceptibility and lung damage associated with a decrease in neutrophil accumulation. This study demonstrated that the IL-22/IL-22BP system plays a major role during Pseudomonas aeruginosa pneumonia by moderating neutrophil accumulation in the lungs that ultimately leads to epithelium protection. Pneumonia induced by Pseudomonas aeruginosa (PA), a Gram-negative opportunistic bacteria, is a major threat for immune-compromised patients 1. During infection, the host must activate a robust but adapted immune response against the pathogen while protecting the integrity and the functionality of the lungs. In the early period of pulmonary infection, there is massive polymorphonuclear neutrophil (PMN) recruitment generating oedema and tissue damage through the generation of an oxidative burst and pro-inflammatory microenvironment. Deregulated and overwhelming activation of PMN can lead to destruction of the alveolar-capillary barrier and to acute respiratory distress syndrome (ARDS) 2. Interleukin (IL)-22 is a member of the IL-10 superfamily and is currently described as the cytokine of epithelium protection.
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Submitted on : Tuesday, April 17, 2018 - 3:31:04 PM
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Alexis Broquet, Cédric Jacqueline, Marion Davieau, Anissa Besbes, Antoine Roquilly, et al.. Interleukin-22 level is negatively correlated with neutrophil recruitment in the lungs in a Pseudomonas aeruginosa pneumonia model. Scientific Reports, Nature Publishing Group, 2017, 7 (1), pp.11010 - 11010. ⟨10.1038/s41598-017-11518-0⟩. ⟨hal-01768933⟩



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