Production of Interleukin-20 cytokines limits bacterial clearance and lung inflammation during infection by Streptococcus pneumoniae

Abstract

Background: Streptococcus pneumoniae is the leading cause of bacterial pneumonia worldwide. Previous reports showed that IL-20 cytokines (IL-19, IL-20 and IL-24) are induced and have an immuno-regulatory function during cutaneous infection. In the current study, our aim was to demonstrate the implication of IL-20 cytokines and their receptors and their role during experimental pneumococcal infection.

Methods: C57BL/6 mice were infected with S. pneumoniae by intranasal route. The bacterial burden, the immune response and the cytokine production were evaluated after treatment with an anti-IL-20 receptor-b (IL-20Rb) neutralizing antibody (anti-IL-20Rb).

Findings: Of interest, expression of IL-20 cytokines mRNA and protein were transiently increased in the lung tissue during infection. Blocking of the IL-20Rb decreased the bacterial burden both in the bronchoalveolar lavage and the lung whereas there was no significant drop in the blood. This treatment also reduced the pulmonary damages (as shown by the alveolar wall thickening), the recruitment of neutrophils and dendritic cells, and the levels of the pro-inflammatory cytokines IL-1β and IL-6 in the lung. Administration of the anti-IL-20Rb antibody enhanced the synthesis of the antibacterial peptide LCN2. However, this effect is transient and did not affect the survival of the infected mice.

Interpretation: Collectively, this study highlights the implication of IL-20 related cytokines during lung infection by S. pneumoniae and might have therapeutic applications in bacterial pneumonia.

Fundings: This work was supported by CNRS, INSERM, INSERM-transfert, the University of Lille and the Fondation du Souffle (Paris, France).

Keywords: Antimicrobial peptides; Cytokine receptor; Cytokines; Immunomodulation; Pneumonia.