Impact of the myeloid Krüppel like factor4 during pneumococcal pneumonia

Streptococcus pneumoniae, the most frequently isolated pathogen from clinical samples of pneumonia, colonizes the human nasopharyngeal mucosa. Pneumonia is the fifth main cause of death in developed countries with as high as 151 million episodes in the developing countries. Krüppel-like factor 4 (KLF4) is a zinc finger containing transcription factor that is involved in the regulation of inflammatory response, tissue homeostasis and regeneration in different cell types and tissues as well as various human diseases. Neutrophils belong to the class of myeloid cells and forms an important component of innate immune system against bacterial infections.

The present study is on the regulation of bacterial pneumonia induced inflammation by myeloid KLF4 in a knockout (KO) mouse model using in vivo as well as in vitro assays. Neutrophils isolated from mice and humans express KLF4 after stimulation with Streptococcus pneumoniae. This KLF4 expression depends on the autolysis of pneumococci. Myeloid KLF4 exhibits a pro-inflammatory phenotype and there was higher bacterial load in the lungs, blood and spleen of infected KLF4 KO mice compared to wildtype (WT) mice. Even though there were lower pro-inflammatory cytokine levels in myeloid KLF4 KO mice, there were no changes in cell recruitment between KLF4 KO and WT mice detectable. Further there was an increased vascular permeability and an earlier death of KLF4 KO mice observable.

These results underline the important immunomodulatory function of KLF4 which may pave the way to innovative adjunctive, host-directed therapeutic options in severe pneumonia.