Toll-Like Receptors Modulate the Host Immune Response to Infection with Salmonella Typhimurium

Salmonella species cause a wide range of disease syndromes in many hosts. In mice S. typhimurium causes a severe invasive disease, similar to those seen in other host species. The lipid A domain of S. typhimurium lipopolysaccharide (LPS) is critical in causing death in mouse typhoid infections, probably via production of high levels of cytokine mediators from macrophages. Macrophage responses are modulated by LPS, live bacteria and bacterial products (e.g. lipoproteins, DNA) which are recognised, at least in part, through Toll-like receptors (TLRs), a group of key regulatory proteins in mammals.<P>
Using TLR knock-out mice this study will investigate the hypothesis that both the protective innate response and the lethality seen in different Salmonella infections in mice, are both dependent on interactions between lipid A and/or other bacterial products and TLRs.