The role of immunostimulatory CpG-DNA in septic shock.

Abstract

Septic shock is the most severe manifestation of infection, and in the intensive care unit (ICU) appears increasingly commonly (reviewed in [20]). As in other forms of acute circulatory failure, septic shock is best described as an imbalance between oxygen demand and oxygen delivery [18]. Older studies suggested that gram-negative bacteria are more commonly associated with septic shock; however, more recent studies have shown that gram-positive bacteria are just as common. Septic shock develops when specific microbial components gain access to the circulation and are recognized by the immune system which generates exaggerated mediator and cytokine responses. Cell wall constituents, such as LPS in gram-negative bacteria, or peptidoglycan and teichoic acid in gram-positive bacteria, or proteins liberated during growth (exotoxins) are considered as the principal microbial components responsible. Exotoxins are a group of bacterial proteins that have been termed superantigens (Sag) because of their unique mechanism to interact with antigen-presenting cells (APCs) and T lymphocytes [14]. All Sag share the ability to bind to MHC class II molecules outside the peptide binding groove as intact proteins. Once bound to MHC class II molecules Sag bind to certain regions of the T cell receptor (TCR) β chain encoded by Vβ gene segments. Consequently a trimolecular TCR-Sag-MHC complex is formed which causes cross-linking and immobilization of the TCR and activation of the respective T cells [17]. Finally, pore-forming bacterial exotoxins may also contribute to the pathogenesis of sepsis syndrome and septic shock [1].