Enterococcus faecalis is one of the most common opportunistic pathogens responsible for nosocomial infections, and its LTA is known as an important virulence factor causing inflammatory responses. As chemokines play a key role in inflammatory diseases by triggering leukocyte infiltration into the infection site, we purified EfLTA and investigated its effect on the expression of chemokines, IP-10, MIP-1α, and MCP-1, in murine macrophages. EfLTA induced the expression of these chemokines at the mRNA and protein levels. TLR2, CD14, and MyD88 were involved in the EfLTA-induced chemokine expression, as the expression was reduced remarkably in macrophages derived from TLR2-, CD14-, or MyD88-deficient mice. EfLTA induced phosphorylation of MAPKs and enhanced the DNA-binding activity of NF-κB, AP-1, and NF-IL6 transcription factors. The induction of IP-10 required ERK, JNK, p38 MAPK, PKC, PTK, PI3K, and ROS. We noticed that all of these signaling molecules, except p38 MAPK and ROS, were indispensable for the induction of MCP-1 and MIP-1α. Interestingly, the EfLTA-induced chemokine expression was mediated through PAFR/JAK/STAT1 signaling pathways without IFN-βinvolvement, which is different from LPS-induced chemokine expression requiring IFN-β/JAK/ STAT1 signaling pathways. Furthermore, the culture supernatant of EfLTA-treated RAW 264.7 cells promoted the platelet aggregation, and exogenous PAF induced the chemokine expression in macrophages derived from WT and TLR2-deficient mice. These results suggest that EfLTA induces the expression of chemokines via signaling pathways requiring TLR2 and PAFR, which is distinct from that of LPS-induced chemokine expression.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Cell Biology