The transcription factor Krueppel-like factor (KLF) 4 fosters the pro-inflammatory immune
response in macrophages and polymorphonuclear neutrophils (PMNs) when stimulated
with Streptococcus pneumoniae, the main causative pathogen of community-acquired
pneumonia (CAP). Here, we investigated the impact of KLF4 expression in myeloid cells
such as macrophages and PMNs on inflammatory response and disease severity in a
pneumococcal pneumonia mouse model and in patients admitted to hospital with CAP.
We found that mice with a myeloid-specific knockout of KLF4 mount an insufficient early
immune response with reduced levels of pro-inflammatory cytokines and increased levels
of the anti-inflammatory cytokine interleukin (IL) 10 in bronchoalveolar lavage fluid and
plasma and an impaired bacterial clearance from the lungs 24 hours after infection with
S. pneumoniae. This results in higher rates of bacteremia, increased lung tissue damage,
more severe symptoms of infection and reduced survival. Higher KLF4 gene expression
levels in the peripheral blood of patients with CAP at hospital admission correlate with a
favourable clinical presentation (lower sequential organ failure assessment (SOFA) score),
lower serum levels of IL-10 at admission, shorter hospital stay and lower mortality or
requirement of intensive care unit treatment within 28 days after admission. Thus, KLF4 in
myeloid cells such as macrophages and PMNs is an important regulator of the early proinflammatory
immune response and, therefore, a potentially interesting target for
therapeutic interventions in pneumococcal pneumonia.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84307 |
| Date | 24 March 2023 |
| Creators | Herta, Toni, Bhattacharyya, Aritra, Rosolowski, Maciej, Conrad, Claudia, Gurtner, Corinne, Gruber, Achim D., Ahnert, Peter, Gutbier, Birgitt, Frey, Doris, Suttorp, Norbert, Hippenstiel, Stefan, Zahlten, Janine |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1664-3224, 726135 |
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