Interleukin-22 regulates interferon lambda expression in a mice model of pseudomonas aeruginosa pneumonia

Background: Interleukin (IL)-22 is a cytokine involved in tissue protection and repair following lung pathologies. Interferon (IFN)-lambda cytokines displayed similar properties during viral infection and a synergy of action between these two players has been documented in the intestine. We hypothesize that during Pseudomonas aeruginosa challenge, IL-22 up-regulates IFN-lambda and that IFN-lambda exhibits protective functions during Pseudomonas aeruginosa acute pneumonia model in mice. Methods: Using an in vitro human alveolar epithelial cell line A549, we assessed the ability of IL-22 to enhance IFN-lambda expression during infection. IFN-lambda protective function was evaluated in an acute mouse pneumonia model. Results: We first demonstrated in murine lungs that only type-II alveolar cells express IL-22 receptor and that IL-22 treatment of A549 cell line up-regulates IFN-lambda expression. In a murine acute pneumonia model, IL-22 administration maintained significant IFN-lambda levels in the broncho-alveolar fluids whereas IL-22 neutralization abolished IFN-lambda up-regulation. In vivo administration of IFN-lambda during Pseudomonas aeruginosa pneumonia improves mice outcome by dampening neutrophil recruitment and decreasing epithelium damages. Discussion: We show here that IL-22 regulates IFN-lambda levels during Pseudomonas aeruginosa pneumonia.