The Innate Immune Response to Bacterial Infection: The Roles of CD14, Lipopolysaccharide Binding Protein (LBP) and Toll-like Receptors (TLR)

The innate immune system represents a first line of defense of our body against infection. Without activation of the innate immune system, invading bacteria for instance rapidly multiply and cause severe infection and death. The initial recognition of bacterial cell wall components serves as a precondition for the induction of such protective immune reactions. Among the recognition receptors involved, CD 14 has attracted particular interest. However, since CD 14 lacks a cytoplasmatic domain, the signal transduction. mechanism leading to the induction of innate immune reactions, remained poorly understood. Recent evidence indicates that signal transduction after binding of bacterial antigens to CD 14 takes place via Toll-like receptors (TLRs). TLRs, named after the toll-receptor of Drosophila, are not only able to recognize bacterial cell wall components but also to induce an inflammatory immune response. Current knowledge of the biological role of TLRs, CD14 and Lipopolysaccharide-Binding- Protein (LBP) is mainly derived from in vitro experiments and from in vivo studies with gene knock-out mice with purified microbial cell wall components. We want to expand these studies and to analyze the biological and clinical relevance of these obviously highly important pattern recognition structures in three informative and clinically important infection models with intact living bacteria. The three planned models are pneumonia, peritonitis and systemic infection to be studied in the respective knock-out mice (CD14, TLR2, TLR4 and LBP -/-). Such knowledge may contribute to the development of new tools to treat severe bacterial infections.