Apolipoprotein B100 is a suppressor of Staphylococcus aureus-induced innate immune responses in humans and mice.
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.
Research Center for Molecular Medicine of Austrian Academy of Sciences, Vienna, Austria.
Stefanie
S
Sigel
Sebastian
S
Bunk
Thomas
T
Meergans
Bianca
B
Doninger
Karin
K
Stich
Thomas
T
Stulnig
Kurt
K
Derfler
Julia
J
Hoffmann
Susanne
S
Deininger
Sonja
S
von Aulock
Sylvia
S
Knapp
D000818:Animals; D053299:Apolipoprotein B-100 / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013047:Specific Pathogen-Free Organisms; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*; D013682:Teichoic Acids / Q000037:antagonists & inhibitors / Q000276:immunology*
D053299:Apolipoprotein B-100; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid