LPS (lipopolysaccharide, endotoxin) susceptibility, an important factor in the innate immune response to Gram-negative bacterial infections. Benefits and hazards of LPS hypersensitivity

点击翻译按钮获取中文摘要

LPS (lipopolysaccharide, endotoxin) is a major component of the outer cell wall of Gram-negative bacteria. LPS plays an important role in the early recognition and in the defense against invading bacteria by the innate immune system. The activation of the innate immune system however, is not without complications for the infected organism. LPS is a potent inducer of many pathophysiological activities seen during infection, including the development of endotoxin shock, frequently with lethal outcome. With the proposed research project it is intended to make a useful contribution to the clarifying of genetic factors determining innate LPS susceptibility and to the understanding of the factors underlying the development of LPS hypersensitivity and its role in the course of infection. The objectives of the study are the following: A. To obtain definite evidence that TLR4 (Toll-like receptor 4) is the central recognition and signaling protein in the activation of cells by LPS. B. To study the involvement of IFN (Interferon)-a/b in the induction of IFN-g and thus in the induction of LPS hypersensitivity in infected host. The pathogen-induced IFN-g represents the key mediator of LPS hypersensitivity that develops during infection. C. To investigate the consequences of an existing LPS hypersensitivity on 1) the resistance to infection and 2) the risk of development of endotoxin shock. Both properties result from an activation of the innate immune system by LPS.