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MicroRNA-223 Dampens Pulmonary Inflammation during Pneumococcal Pneumonia.

ABSTRACT: Community-acquired pneumonia remains a major contributor to global communicable disease-mediated mortality. Neutrophils play a leading role in trying to contain bacterial lung infection, but they also drive detrimental pulmonary inflammation, when dysregulated. Here we aimed at understanding the role of microRNA-223 in orchestrating pulmonary inflammation during pneumococcal pneumonia. Serum microRNA-223 was measured in patients with pneumococcal pneumonia and in healthy subjects. Pulmonary inflammation in wild-type and microRNA-223-knockout mice was assessed in terms of disease course, histopathology, cellular recruitment and evaluation of inflammatory protein and gene signatures following pneumococcal infection. Low levels of serum microRNA-223 correlated with increased disease severity in pneumococcal pneumonia patients. Prolonged neutrophilic influx into the lungs and alveolar spaces was detected in pneumococci-infected microRNA-223-knockout mice, possibly accounting for aggravated histopathology and acute lung injury. Expression of microRNA-223 in wild-type mice was induced by pneumococcal infection in a time-dependent manner in whole lungs and lung neutrophils. Single-cell transcriptome analyses of murine lungs revealed a unique profile of antimicrobial and cellular maturation genes that are dysregulated in neutrophils lacking microRNA-223. Taken together, low levels of microRNA-223 in human pneumonia patient serum were associated with increased disease severity, whilst its absence provoked dysregulation of the neutrophil transcriptome in murine pneumococcal pneumonia.

SUBMITTER: Goekeri C

PROVIDER: S-EPMC10047070 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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MicroRNA-223 Dampens Pulmonary Inflammation during Pneumococcal Pneumonia.

Goekeri Cengiz C Pennitz Peter P Groenewald Wibke W Behrendt Ulrike U Kirsten Holger H Zobel Christian M CM Berger Sarah S Heinz Gitta A GA Mashreghi Mir-Farzin MF Wienhold Sandra-Maria SM Dietert Kristina K Dorhoi Anca A Gruber Achim D AD Scholz Markus M Rohde Gernot G Suttorp Norbert N Capnetz Study Group Witzenrath Martin M Nouailles Geraldine G

Cells 20230321 6

Community-acquired pneumonia remains a major contributor to global communicable disease-mediated mortality. Neutrophils play a leading role in trying to contain bacterial lung infection, but they also drive detrimental pulmonary inflammation, when dysregulated. Here we aimed at understanding the role of microRNA-223 in orchestrating pulmonary inflammation during pneumococcal pneumonia. Serum microRNA-223 was measured in patients with pneumococcal pneumonia and in healthy subjects. Pulmonary infl ...[more]

PMID: 36980300

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Project description:BackgroundPeople with chronic obstructive pulmonary disease (COPD) are at increased risk of pneumococcal disease, especially pneumonia, as well as acute exacerbations with associated morbidity and healthcare costs.ObjectivesTo determine the efficacy of injectable pneumococcal vaccination for preventing pneumonia in persons with COPD.Search methodsWe searched the Cochrane Airways COPD Trials Register and the databases CENTRAL, MEDLINE and Embase, using prespecified terms. Searches are current to November 2016.Selection criteriaWe included randomised controlled trials (RCT) comparing injectable pneumococcal polysaccharide vaccine (PPV) or pneumococcal conjugated vaccine (PCV) versus a control or alternative vaccine type in people with COPD.Data collection and analysisWe used standard Cochrane methodological procedures. For meta-analyses, we subgrouped studies by vaccine type.Main resultsFor this update, we added five studies (606 participants), meaning that the review now includes a total of 12 RCTs involving 2171 participants with COPD. Average age of participants was 66 years, male participants accounted for 67% and mean forced expiratory volume in one second (FEV1) was 1.2 L (five studies), 54% predicted (four studies). We assessed risks of selection, attrition and reporting bias as low, and risks of performance and detection bias as moderate.Compared with control, the vaccine group had a lower likelihood of developing community-acquired pneumonia (CAP) (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.43 to 0.89; six studies, n = 1372; GRADE: moderate), but findings did not differ specifically for pneumococcal pneumonia (Peto OR 0.26, 95% CI 0.05 to 1.31; three studies, n = 1158; GRADE: low). The number needed to treat for an additional beneficial outcome (NNTB) (preventing one episode of CAP) was 21 (95% CI 15 to 74). Mortality from cardiorespiratory causes did not differ between vaccine and control groups (OR 1.07, 95% CI 0.69 to 1.66; three studies, n = 888; GRADE: moderate), nor did all-cause mortality differ (OR 1.00, 95% CI 0.72 to 1.40; five studies, n = 1053; GRADE: moderate). The likelihood of hospital admission for any cause, or for cardiorespiratory causes, did not differ between vaccine and control groups. Vaccination significantly reduced the likelihood of a COPD exacerbation (OR 0.60, 95% CI 0.39 to 0.93; four studies, n = 446; GRADE: moderate). The NNTB to prevent a patient from experiencing an acute exacerbation was 8 (95% CI 5 to 58). Only one study (n = 181) compared the efficacy of different vaccine types - 23-valent PPV versus 7-valent PCV - and reported no differences for CAP, all-cause mortality, hospital admission or likelihood of a COPD exacerbation, but investigators described a greater likelihood of some mild adverse effects of vaccination with PPV-23.Authors' conclusionsInjectable polyvalent pneumococcal vaccination provides significant protection against community-acquired pneumonia, although no evidence indicates that vaccination reduced the risk of confirmed pneumococcal pneumonia, which was a relatively rare event. Vaccination reduced the likelihood of a COPD exacerbation, and moderate-quality evidence suggests the benefits of pneumococcal vaccination in people with COPD. Evidence was insufficient for comparison of different pneumococcal vaccine types.

Dataset Information

MicroRNA-223 Dampens Pulmonary Inflammation during Pneumococcal Pneumonia.

Publications

MicroRNA-223 Dampens Pulmonary Inflammation during Pneumococcal Pneumonia.

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