Receptor polymorphisms and non-classical bacterial immune stimuli
Variants of the human TLR4 and of the bacterial surface molecules LPS and LTA - their specific roles in innate immunity
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The courses of infections, ranging from subclinical to lethal diseases, are determined by numerous variables of the host defence and of the nature of the pathogens. Genetic polymorphisms of both regulatory promoter and coding sequences are increasingly linked with disease susceptibility and outcome. The first part of this study is attributed to a variant of one of the human pattern recognition receptors, which constitute key elements for the initiation of an innate immune response. We elucidate the effects of the human heterozygous TLR4 Asp(299)Gly polymorphism on cytokine release and examine ...
The courses of infections, ranging from subclinical to lethal diseases, are determined by numerous variables of the host defence and of the nature of the pathogens. Genetic polymorphisms of both regulatory promoter and coding sequences are increasingly linked with disease susceptibility and outcome. The first part of this study is attributed to a variant of one of the human pattern recognition receptors, which constitute key elements for the initiation of an innate immune response. We elucidate the effects of the human heterozygous TLR4 Asp(299)Gly polymorphism on cytokine release and examine whether they play a role in Crohn's Disease. The focus of the second part is the functional analysis of non-classical bacterial surface components, which are crucial for the initiation of immune defence mechanisms and which also determine the extent of inflammatory reactions. Hereby we examine the endotoxic properties of special lipo-polysaccharide and lipo-teichoic acid variants. This work wants to contribute to the understanding of the consequences of molecular variations for host-pathogen interaction and immune defence.
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