Bacterial DNA is characterized by unmethylated Cytosin-Guanosin-dinucleotides (CpG-DNA), which interact with Toll-like receptor 9 (TLR9). CpG-DNA as well as oligonucleotides containing a CpG motif have been shown to cause septic shock in vivo. However, it is not known whether TLR9 signalling in cardiac myocytes contributes to septic shock. Therefore, we investigated sarcomere shortening of isolated cardiac myocytes of wild-type (WT, C57BL/6) and TLR9-deficient (TLR9^-/-) mice kept in a short-term culture (up to 6 h) with or without CpG-DNA (1 mM, oligonucleotide 1668, Sparwasser et al., 1997, Nature 386). Sarcomere shortening was elicited externally (0.5–10 Hz) and recorded by a video imaging system. Sarcomere shortening amplitude was not significantly changed after 6 h of culture in comparison to control conditions. However, application of CpG-DNA reduced sarcomere shortenings of WT cells significantly after more than 3 h incubation time, whereas shortening of TLR9^-/-cells was insensitive to CpG-DNA. In the average, shortening of WT cells was depressed by about 38% after 5 h. Thus, we could demonstrate that the influence of CpG-DNA leads to a depression of cardiac contractility. The effect depends on TLR9 expression. Interaction with immune cells is not necessary to induce cardiac depression in sepsis caused by bacterial DNA,

i.e. the whole signalling cascade is present in cardiac myocytes.