Comparative characterization of bacterial immune stimuli

Abstract

The immune system responds to invading pathogens with a broad spectrum of inflammatory reactions. The pathogens are recognized by different immune cells via the pathogen recognition receptors. These pathogen recognition receptors detect conserved structures of pathogens, the pathogen-associated molecular patterns. The pathogen-associated molecular patterns are structures of the bacterial cell wall or intracellular molecules. Eminent structures from Gram-negative bacteria are lipopolysaccharide, peptidoglycan and bacterial DNA, while conserved structures from Gram-positive bacteria are lipoteichoic acid, peptidoglycan as well as bacterial DNA. Naturally occurring breakdown products of peptidoglycan are called muropeptides. One prominent muropeptide is muramyl dipeptide, which is known as minimal principle for adjuvant activity.In this work a comparative characterization of whole Staphylococcus aureus, lipoteichoic acid, bacterial DNA, peptidoglycan and muropeptides have been carried out. This work shows that lipoteichoic acid is the main immunostimulatory principle of Staphylococcus aureus. Muramyl dipeptide and other muropeptides synergize in cytokine induction with lipopolysaccharide and bacterial DNA. The structural requirements and the mechanism of synergy of lipopolysaccharide and bacterial DNA with muramyl dipeptide have been characterized. These findings add to our understanding of bacterial immune recognition by the innate immune system.