Publikationsdatenbank

MicroRNA-223 Dampens Pulmonary Inflammation during Pneumococcal Pneumonia (2023)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Goekeri, Cengiz

Pennitz, Peter

Groenewald, Wibke

Behrendt, Ulrike

Kirsten, Holger

Zobel, Christian M.

Berger, Sarah

Heinz, Gitta A.

Mashreghi, Mir-Farzin

Wienhold, Sandra-Maria

Dietert, Kristina (WE 12)

Dorhoi, Anca

Gruber, Achim D. (WE 12)

Scholz, Markus

Rohde, Gernot

Suttorp, Norbert

Capnetz Study Group

Witzenrath, Martin

Nouailles, Geraldine

Quelle

Cells : open access journal

Bandzählung: 12

Heftzählung: 6

Seiten: 1 – 13

ISSN: 2073-4409

Sprache

Englisch

Verweise

URL (Volltext): https://pubmed.ncbi.nlm.nih.gov/36980300/

DOI: 10.3390/cells12060959

Pubmed: 36980300

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.