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- Title
MicroRNA-223 Dampens Pulmonary Inflammation during Pneumococcal Pneumonia.
- Authors
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; Dorhoi, Anca; Gruber, Achim D.; Scholz, Markus; Rohde, Gernot; Suttorp, Norbert; Witzenrath, Martin; Nouailles, Geraldine
- 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.
- Subjects
PNEUMOCOCCAL pneumonia; STREPTOCOCCAL diseases; BACTERIAL diseases; COMMUNITY-acquired pneumonia; INFLAMMATION; LUNG infections
- Publication
Cells (2073-4409), 2023, Vol 12, Issue 6, p959
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells12060959