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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-1? 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).

SUBMITTER: Madouri F

PROVIDER: S-EPMC6284423 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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

Madouri Fahima F Barada Olivia O Kervoaze Gwenola G Trottein François F Pichavant Muriel M Gosset Philippe P

EBioMedicine 20181022

<h4>Background</h4>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.<h4>Methods</h4>C57BL/6 mice were infected with S. pneumoniae by intranasal route. The bac ...[more]

PMID: 30361066

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Project description:UnlabelledThe transmission of the bacterium Streptococcus pneumoniae (the pneumococcus) marks the first step toward disease development. To date, our ability to prevent pneumococcal transmission has been limited by our lack of understanding regarding the factors which influence the spread of this pathogen. We have previously developed an infant mouse model of pneumococcal transmission which was strictly dependent on influenza A virus (IAV) coinfection of both the experimentally colonized "index mice" and the naive cohoused "contact mice." Here, we sought to use this model to further elucidate the factors which facilitate S. pneumoniae transmission. In the present report, we demonstrate that increasing the nasopharyngeal load of S. pneumoniae in the colonized index mice (via the depletion of neutrophils) and inducing a proinflammatory response in the naive cohoused contact mice (as demonstrated by cytokine production) facilitates S. pneumoniae transmission. Thus, these data provide the first insights into the factors that help mediate the spread of S. pneumoniae throughout the community.ImportanceStreptococcus pneumoniae (the pneumococcus) is a major cause of worldwide morbidity and mortality and is a leading cause of death among children under the age of five years. Transmission of S. pneumoniae marks the first step toward disease development. Therefore, understanding the factors that influence the spread of pneumococci throughout the community plays an essential role in preventing pneumococcal disease. We previously developed the first reproducible infant mouse model for pneumococcal transmission and showed that coinfection with influenza virus facilitates the spread of S. pneumoniae. Here, we show that increasing the bacterial load in the nasal cavity of colonized individuals as well as inducing an inflammatory response in naive "contact cases" facilitates the spread of pneumococci. Therefore, this study helps to identify the factors which must be inhibited in order to successfully prevent pneumococcal disease.

Dataset Information

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

Publications

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

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