Im Rahmen dieser Studie konnte der Transkriptionsfaktor KLF4 als ein wichtiger Regulator des antiinflammatorischen Mediators IL-10 in humanen Lungenepithelzellen nach Stimulation mit S. pneumoniae identifiziert werden. Gleichzeitig konnte eine Beteiligung des TLR9 und der Src Proteintyrosinkinasen an der S. pneumoniae induzierten IL-10 Sekretion herausgearbeitet werden.
Although the release of potent pro-inflammatory mediators is central for mounting an efficient host response in infections, excessive inflammation may lead to deleterious tissue damage. This is highlighted in severe pneumococcal pneumonia, in which the delicate balance among a robust inflammatory response to kill pneumococci and loss of organ function determines outcome of disease. Therefore we assessed the regulation of the potent anti-inflammatory cytokine IL-10 in pneumococci infection. S. pneumoniae induced IL-10 expression in mice lungs and human lung epithelial cells. Pneumococcal infection resulted in strong induction of Krüppel-like factor 4- (KLF4) expression in vivo, and in vitro. Both, induction of IL-10 and KLF4, are mediated by a pathway involving bacterial DNA, TLR9, MyD88, and Src kinase. Expressed KLF4 is recruited to the il10 gene promoter, and silencing of KLF4 expression blocked IL-10 expression. In conclusion, KLF4 is induced in a bacterial DNA-TLR9-Src-dependent manner and regulates IL-10 expression, linking the detection of bacterial DNA by TLR9 to the control of an inflammatory response.
