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.

The role of IL‐22 in the resolution of sterile and nonsterile inflammation

“…98 However, this dose is 1000-fold >0.1 mg kg À1 used to induce a protective effect in the high-fat diet murine model. 88 It also contrasts with a murine model study of IL-22's role in Pseudomonas aeruginosa lung damage, 100 where neutralisation of IL-22 resulted in increased neutrophil infiltration, and lung damage. 100 The protection in this study followed treatment with 0.1 mg kg À1 of rIL-22 via intratracheal administration 18 hours prior to induction of acute pneumonia with the bacterium.…”

“…88 It also contrasts with a murine model study of IL-22's role in Pseudomonas aeruginosa lung damage, 100 where neutralisation of IL-22 resulted in increased neutrophil infiltration, and lung damage. 100 The protection in this study followed treatment with 0.1 mg kg À1 of rIL-22 via intratracheal administration 18 hours prior to induction of acute pneumonia with the bacterium. 100 Similarly, a study of rIL-22 treatment in an airway disease model triggered by inhalation of methacholine 78 reported that IL-22 was protective at the more physiological dose of 0.1-10 mg kg À1 .…”

“…98 However, this dose is 1000-fold >0.1 mg kg À1 used to induce a protective effect in the high-fat diet murine model. 100 The protection in this study followed treatment with 0.1 mg kg À1 of rIL-22 via intratracheal administration 18 hours prior to induction of acute pneumonia with the bacterium. 100 The protection in this study followed treatment with 0.1 mg kg À1 of rIL-22 via intratracheal administration 18 hours prior to induction of acute pneumonia with the bacterium.…”

“…100 The protection in this study followed treatment with 0.1 mg kg À1 of rIL-22 via intratracheal administration 18 hours prior to induction of acute pneumonia with the bacterium. 100 Similarly, a study of rIL-22 treatment in an airway disease model triggered by inhalation of methacholine 78 reported that IL-22 was protective at the more physiological dose of 0.1-10 mg kg À1 . 78 Unlike the smoke inhalation study, the finding of rIL-22 protection was supported by IL-22 KO mice, which developed more inflammation following methacholine challenge.…”

Targeting the IL-22/IL-22BP axis enhances tight junctions and reduces inflammation during influenza infection

“…15 Neutralizing IL-22BP in the lung significantly increases survival and decreases neutrophilia in a mouse model of Pseudomonas aeruginosa. 16 Under naive conditions in the lung, alveolar epithelial cells and alveolar macrophages (AMs) have been identified as sources of IL-22BP, 17,18 and neutrophils are a source during catastrophic lung injury. 18 In the current study, we demonstrate that shifting the balance of the IL-22/IL-22BP axis in favor of IL-22 promotes recovery during influenza infection by promoting tight junction formation.…”