Apolipoprotein B100 is a suppressor of Staphylococcus aureus‐induced innate immune responses in humans and mice

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2012
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Sigel, Stefanie
Bunk, Sebastian
Doninger, Bianca
Stich, Karin
Stulnig, Thomas
Derfler, Kurt
Hoffmann, Julia
Deininger, Susanne
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European Journal of Immunology. Wiley. 2012, 42(11), pp. 2983-2989. ISSN 0014-2980. eISSN 1521-4141. Available under: doi: 10.1002/eji.201242564
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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, ApoA1, and ApoA2. Only ApoB100 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 ApoB100‐directed immuno‐apheresis confirmed that ApoB100 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 ApoB100 as an important suppressor of innate immune activation in response to S. aureus and its LTA.

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ISO 690SIGEL, Stefanie, Sebastian BUNK, Thomas MEERGANS, Bianca DONINGER, Karin STICH, Thomas STULNIG, Kurt DERFLER, Julia HOFFMANN, Susanne DEININGER, Sonja von AULOCK, Sylvia KNAPP, 2012. Apolipoprotein B100 is a suppressor of Staphylococcus aureus‐induced innate immune responses in humans and mice. In: European Journal of Immunology. Wiley. 2012, 42(11), pp. 2983-2989. ISSN 0014-2980. eISSN 1521-4141. Available under: doi: 10.1002/eji.201242564
BibTex
@article{Sigel2012-11Apoli-49287,
  year={2012},
  doi={10.1002/eji.201242564},
  title={Apolipoprotein B100 is a suppressor of Staphylococcus aureus‐induced innate immune responses in humans and mice},
  number={11},
  volume={42},
  issn={0014-2980},
  journal={European Journal of Immunology},
  pages={2983--2989},
  author={Sigel, Stefanie and Bunk, Sebastian and Meergans, Thomas and Doninger, Bianca and Stich, Karin and Stulnig, Thomas and Derfler, Kurt and Hoffmann, Julia and Deininger, Susanne and Aulock, Sonja von and Knapp, Sylvia}
}
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