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Apolipoprotein B 100 is a suppressor of S taphylococcus aureus‐induced innate immune responses in humans and mice
Author(s) -
Sigel Stefanie,
Bunk Sebastian,
Meergans Thomas,
Doninger Bianca,
Stich Karin,
Stulnig Thomas,
Derfler Kurt,
Hoffmann Julia,
Deininger Susanne,
von Aulock Sonja,
Knapp Sylvia
Publication year - 2012
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201242564
Subject(s) - innate immune system , biology , immune system , suppressor , apolipoprotein b , immunology , microbiology and biotechnology , genetics , gene , cholesterol , endocrinology
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 S taphylococcus 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 ( A po) B 100, A po A 1, and A po A 2. Only A po B 100 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 A po B 100‐directed immuno‐apheresis confirmed that A po B 100 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 A po B 100 as an important suppressor of innate immune activation in response to S . aureus and its LTA .