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- Title
Apolipoprotein B100 is a suppressor of Staphylococcus aureus-induced innate immune responses in humans and mice.
- Authors
Sigel, Stefanie; Bunk, Sebastian; Meergans, Thomas; Doninger, Bianca; Stich, Karin; Stulnig, Thomas; Derfler, Kurt; Hoffmann, Julia; Deininger, Susanne; von Aulock, Sonja; Knapp, Sylvia
- Abstract
Plasma lipoproteins such as LDL (low-density lipoprotein) are important therapeutic targets as they play a crucial role in macrophage biology and metabolic disorders. The impact of lipoprotein profiles on host defense pathways against Gram-positive bacteria is poorly understood. In this report, we discovered that human serum lipoproteins bind to lipoteichoic acid ( LTA) from Staphylococcus aureus and thereby alter the immune response to these bacteria. Size-exclusion chromatography and solid-phase-binding analysis of serum revealed the direct interaction of LTA with apolipoproteins ( Apo) B100, Apo A1, and Apo A2. Only Apo B100 and the corresponding LDL exerted biological effects as this binding significantly inhibited LTA-induced cytokine releases from human and murine immune cells. Serum from hypercholesterolemic mice or humans significantly diminished cytokine induction in response to S. aureus or its LTA. Sera taken from the patients with familial hypercholesterolemia before and after Apo B100-directed immuno-apheresis confirmed that Apo B100 inhibited LTA-induced inflammation in humans. In addition, mice in which LDL secretion was pharmacologically inhibited, displayed significantly increased serum cytokine levels upon infection with S. aureus in vivo. The present study identifies Apo B100 as an important suppressor of innate immune activation in response to S. aureus and its LTA.
- Publication
European Journal of Immunology, 2012, Vol 42, Issue 11, p2983
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201242564