MicroRNA-223 Dampens Pulmonary Inflammation during Pneumococcal Pneumonia
2023
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 | Group:, CAPNETZ Study | Witzenrath, Martin | Nouailles, Geraldine
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.
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书目信息
出版者 MDPI (Multidisciplinary Digital Publishing Institute)
ISSN 2073-4409