Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin

Knippenberg, Sarah; Ueberberg, Bianca; Maus, Regina; Bohling, Jennifer; Ding, Nadine; Tarrés, Meritxell Tort; Hoymann, Heinz-Gerd; Jonigk, Danny; Izykowski, Nicole; Paton, James C.; Ogunniyi, Abiodun D.; Lindig, Sandro; Bauer, Michael; Welte, Tobias; Seeger, Werner; Güenther, Andreas; Sisson, Thomas H.; Gauldie, Jack; Kolb, Martin; Maus, Ulrich A.

doi:10.1136/thoraxjnl-2014-206420

Cited by 75 publications

(77 citation statements)

References 35 publications

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“…Based on our examination at diagnosis, the occurrence of an AE in the future was not related to an increased total bacterial burden and the loss of diversity (Additional File 1: Figure S1). However, because this study highlighted the possibility of the effect of microbiomes on AEs [21][22][23], we intend to elucidate these findings in our next larger prospective study. Furthermore, we believe that it is imperative to investigate the causative bacteria on fibrosis in a murine model in the future.…”

Section: Discussionmentioning

confidence: 99%

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis

et al. 2018

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Background: Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. Although IPF has not been thought to be associated with bacterial communities, recent papers reported the possible role of microbiome composition in IPF. The roles of microbiomes in respiratory functions and as clinical biomarkers for IPF remain unknown. In this study, we aim to identify the relationship between the microbial environment in the lung and clinical findings. Methods: Thirty-four subjects diagnosed with IPF were included in this analysis. The 16S rDNA was purified from bronchoalveolar lavage fluid obtained at the time of diagnosis and analyzed using next-generation sequencing techniques to characterize the bacterial communities. Furthermore, microbiomes from mice with bleomycininduced lung fibrosis were analyzed.

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Section: Discussionmentioning

confidence: 99%

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis

et al. 2018

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“…Interestingly, recent work suggests Streptococcus pneumolysin exacerbates lung fibrosis in murine models (44).…”

Section: Inflammatory Leukocyte Phenotypes Associate With Microbial Mmentioning

confidence: 99%

Microbes Are Associated with Host Innate Immune Response in Idiopathic Pulmonary Fibrosis

Huang

Fan

Espíndola

et al. 2017

Am J Respir Crit Care Med

120

106

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“…While human data is lacking, two separate mouse models of pulmonary fibrosis and Streptococcus pnemoniae infection suggest that prompt antibiotic administration following infection attenuates subsequent fibrosis exacerbation. (8) In the same report, immunization against the pneumococcal virulence factor, pneumolysin, prevents fibrosis exacerbation. (8) Additional work is needed to determine the mechanism by which specific organisms result in propagation of fibrosis, and the role of immunization and antibiotics in limiting their impact on disease progression in humans with IPF.…”

Section: From Lung Microbiome Alterations To Treatment Strategies In Ildmentioning

confidence: 97%

“…are associated with increased risk of disease progression in humans is in line with the findings in two separate mouse models, where infection with Streptococcus pneumoniae results in exacerbation of existing lung fibrosis. (8)…”

Section: An Altered Lung Microbiome Predicts Disease Progression In Ipfmentioning

confidence: 99%

“…(5–7) These observations, along with studies suggesting that antibiotic administration or immunization against pathogenic organisms may improve IPF outcomes,(8, 9) have created enthusiasm for evaluation of the lung microbiome as a therapeutic target. While most research to date has focused on IPF specifically, we are also now beginning to understand the composition of the lung microbiome in other ILDs.…”

Section: Introductionmentioning

confidence: 99%

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Microbiome in interstitial lung disease

Salisbury

Han

Dickson

et al. 2017

Current Opinion in Pulmonary Medicine

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Purpose of Review This review summarizes current knowledge of the role of the lung microbiome in interstitial lung disease and poses considerations of the microbiome as a therapeutic target. Recent Findings While historically considered sterile, bacterial communities have now been well documented in lungs in health and disease. Studies in idiopathic pulmonary fibrosis (IPF) suggest that increased bacterial burden and/or abundance of potentially pathogenic bacteria may drive disease progression, acute exacerbations, and mortality. More recent work has highlighted the interaction between the lung microbiome and the innate immune system in IPF, strengthening the argument for the role of both host and environment interaction in disease pathogenesis. In support of this, studies of interstitial lung diseases other than IPF suggest that it may be the host immune response which shapes the microbiome in these diseases. Some clinical and mouse model data also suggest that the lung microbiome may represent a therapeutic target, via antibiotic administration, immunization against pathogenic organisms, or treatment directed at gastroesophageal reflux. Summary Evidence suggests that the lung microbiome may serve as a prognostic biomarker, a therapeutic target, or provide an explanation for disease pathogenesis in IPF.

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Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin

Abstract: Our data unravel a novel mechanism by which infection with Spn through Ply release induces progression of established lung fibrosis, which can be attenuated by protein-based vaccination of mice.

Cited by 75 publications

References 35 publications

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis

Microbes Are Associated with Host Innate Immune Response in Idiopathic Pulmonary Fibrosis

Microbiome in interstitial lung disease

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