Kruppel-like factor 4 regulates neutrophil activation

Abstract

Key Points KLF4 deficiency impairs neutrophil function in vitro and in vivo. This is the first demonstration that KLF4 plays a crucial role in neutrophils.

Impact of the myeloid Krüppel like factor4 during pneumococcal pneumonia

“…The higher mortality of KLF4 -/mice in comparison to KLF4 +/+ mice during S. pneumoniae induced pneumonia are in line with the findings from Shen et al: they had reported earlier that KLF4 KO mice have lower survivability with respect to WT mice after infection with E. coli 166 . Previous reports have described that in order to understand the progression of pneumococcal pneumonia in a murine model, the mice have to be monitored 10 days after infection 177,229 .…”

“…15 and 16 respectively. The results support the hypothesis and by findings from Shen et al which shows that pro-inflammatory factors such as myeloidperoxidase (MPO) and matrix metallopeptidase (MMP)-9 are produced to a less extent in the myeloid KLF4 KO mice during infection 166 . In addition, in vitro studies supported a potential pro-inflammatory phenotype of KLF4 positive cells in BMMs: KLF4 KO in BMMs decreased TNF-α, IL-1β, IL-6 while increased IL-10 production during pneumococcal pneumonia 169 .…”

“…KLF4 -/mice had higher bacterial load in the lungs, blood and in the spleen at 24h post infection compared to the KLF4 +/+ mice from the CFU experiments in Fig. 14, which is supported by a recent report 166 . In this publication, Shen et al had reported higher bacterial load in the blood and peritoneal fluid of myeloid KLF4 KO mice with respect to WT mice in an E. coli sepsis model.…”

“…The difference in the outcome of the present findings may be because they used different bacteria (S. pneumoniae versus Staphylococcus aureus)163 . In line with the observation in that study,Shen et al have reported that bone marrow derived KLF4 KO neutrophils failed to kill E. coli166 . S. pneumoniae initially interacts with the alveolar epithelial cells and the resident macrophages within the lung which in turn induces the chemotactic gradient for neutrophil sequestration at the site of infection91 .…”

“…With the production of less cytokine, it was expected that there would have been less neutrophil recruitment in the BALF and in the plasma 91,166 . However, in the present study, a less neutrophil recruitment was seen only in the blood but not in the BALF as given in Fig.…”