Improving Pulmonary Immunity to Bacterial Pathogens through Streptococcus pneumoniae Colonization of the Nasopharynx.
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ABSTRACT:
SUBMITTER: Brown JS
PROVIDER: S-EPMC6999096 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Publications
Improving Pulmonary Immunity to Bacterial Pathogens through <i>Streptococcus pneumoniae</i> Colonization of the Nasopharynx.
American journal of respiratory and critical care medicine 20200201 3
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Project description:Background and objectiveRespiratory syncytial virus (RSV) is the most significant cause of acute respiratory infection (ARI) in early life. RSV and other respiratory viruses are known to stimulate substantial outgrowth of potentially pathogenic bacteria in the upper airways of young children. However, the clinical significance of interactions between viruses and bacteria is currently unclear. The present study aimed to clarify the effect of viral and bacterial co-detections on disease severity during paediatric ARI.MethodsNasopharyngeal aspirates from children under 2 years of age presenting with ARI to the emergency department were screened by quantitative PCR for 17 respiratory viruses and the bacterial pathogens Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Associations between pathogen detection and clinical measures of disease severity were investigated.ResultsRSV was the most common virus detected, present in 29 of 58 samples from children with ARI (50%). Detection of S. pneumoniae was significantly more frequent during RSV infections compared to other respiratory viruses (adjusted effect size: 1.8, P: 0.03), and co-detection of both pathogens was associated with higher clinical disease severity scores (adjusted effect size: 1.2, P: 0.03).ConclusionCo-detection of RSV and S. pneumoniae in the nasopharynx was associated with more severe ARI, suggesting that S. pneumoniae colonization plays a pathogenic role in young children.
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Project description:We evaluated the effectiveness of anti-22F serotype immunity in the prevention of Streptococcus pneumoniae (Spn) bacterial transmission during colonization and influenza virus co-infection. Mice were immunized with 22F formulation and later colonized with Spn or co-infected with Spn and influenza virus. The 22F antisera exhibited strong reactivity to 22F bacteria and promoted the opsonic uptake of Spn by the neutrophils. The 22F vaccination led to a significant reduction of bacterial densities in the nasopharynx and prevented bacterial transmission during colonization and co-infection. The transfer of 22F antisera to infant mice resulted in reduced bacterial transmission in colonization and co-infection models.
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Project description:RationaleRespiratory tract infections are common in patients suffering from pulmonary fibrosis. The interplay between bacterial infection and fibrosis is characterised poorly.ObjectivesTo assess the effect of Gram-positive bacterial infection on fibrosis exacerbation in mice.MethodsFibrosis progression in response to Streptococcus pneumoniae was examined in two different mouse models of pulmonary fibrosis.Measurements and main resultsWe demonstrate that wild-type mice exposed to adenoviral vector delivery of active transforming growth factor-β1 (TGFß1) or diphteria toxin (DT) treatment of transgenic mice expressing the DT receptor (DTR) under control of the surfactant protein C (SPC) promoter (SPC-DTR) to induce pulmonary fibrosis developed progressive fibrosis following infection with Spn, without exhibiting impaired lung protective immunity against Spn. Antibiotic treatment abolished infection-induced fibrosis progression. The cytotoxin pneumolysin (Ply) of Spn caused this phenomenon in a TLR4-independent manner, as Spn lacking Ply (SpnΔply) failed to trigger progressive fibrogenesis, whereas purified recombinant Ply did. Progressive fibrogenesis was also observed in AdTGFβ1-exposed Ply-challenged TLR4 KO mice. Increased apoptotic cell death of alveolar epithelial cells along with an attenuated intrapulmonary release of antifibrogenic prostaglandin E2 was found to underlie progressive fibrogenesis in Ply-challenged AdTGFβ1-exposed mice. Importantly, vaccination of mice with the non-cytotoxic Ply derivative B (PdB) substantially attenuated Ply-induced progression of lung fibrosis in AdTGFβ1-exposed mice.ConclusionsOur 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.
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