skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Presentation matters: Impact of association of amphiphilic LPS with serum carrier proteins on innate immune signaling

Abstract

Recognition of Pathogen-associated Molecular Patterns (PAMPs) by Toll-like receptors is central to innate immunity. Many bacterial PAMPs such as lipopolysaccharide (LPS) and lipoteichoic acid have amphiphilic properties. The hydrophobicity of amphiphilic PAMPs contributes to increasing entropy and causes these molecules to self-aggregate or bind host carrier proteins in aqueous physiological environments. The goal of this work was to determine how innate immune signaling is impacted by physical presentation and association of amphiphilic PAMPs with serum carrier proteins, using LPS as an example molecule. Specifically, we measured LPS-induced cytokine profiles in murine macrophages when the antigen was presented associated with the various serum carrier proteins in serum versus a serum-depleted system. Our study demonstrates that the observed cytokine profiles are dramatically different when LPS is presented in buffer, versus in serum when it is associated with proteins, specifically with respect to inhibition of pro-inflammatory cytokines in the latter. These studies suggest that LPS-mediated cytokine expression is dependent on its presentation in physiological systems. The amphiphilicity of bacterial PAMPs and consequent association with lipoproteins is a feature, which should be taken into account in the design of in vitro experiments. Further studies of the interdependencies of different serum carriers can identify pathwaysmore » for drug delivery and diagnostics.« less

Authors:
; ; ORCiD logo; ; ; ORCiD logo;
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA); LANL Laboratory Directed Research and Development (LDRD) Program; USDA National Inst. of Food and Agriculture (NIFA)
OSTI Identifier:
1454322
Alternate Identifier(s):
OSTI ID: 1475350
Report Number(s):
LA-UR-17-27524
Journal ID: ISSN 1932-6203; 10.1371/journal.pone.0198531
Grant/Contract Number:  
AC52-06NA25396; 2012-68003-30155
Resource Type:
Published Article
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Name: PLoS ONE Journal Volume: 13 Journal Issue: 6; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; cytokines; serum proteins; inflammation; lipoproteins; macrophages; immune receptor signaling; chemokines; cellular stress responses

Citation Formats

Stromberg, Loreen R., Mendez, Heather M., Kubicek-Sutherland, Jessica Z., Graves, Steven W., Hengartner, Nicolas W., Mukundan, Harshini, and Bernardino de la Serna, ed., Jorge. Presentation matters: Impact of association of amphiphilic LPS with serum carrier proteins on innate immune signaling. United States: N. p., 2018. Web. https://doi.org/10.1371/journal.pone.0198531.
Stromberg, Loreen R., Mendez, Heather M., Kubicek-Sutherland, Jessica Z., Graves, Steven W., Hengartner, Nicolas W., Mukundan, Harshini, & Bernardino de la Serna, ed., Jorge. Presentation matters: Impact of association of amphiphilic LPS with serum carrier proteins on innate immune signaling. United States. https://doi.org/10.1371/journal.pone.0198531
Stromberg, Loreen R., Mendez, Heather M., Kubicek-Sutherland, Jessica Z., Graves, Steven W., Hengartner, Nicolas W., Mukundan, Harshini, and Bernardino de la Serna, ed., Jorge. Thu . "Presentation matters: Impact of association of amphiphilic LPS with serum carrier proteins on innate immune signaling". United States. https://doi.org/10.1371/journal.pone.0198531.
@article{osti_1454322,
title = {Presentation matters: Impact of association of amphiphilic LPS with serum carrier proteins on innate immune signaling},
author = {Stromberg, Loreen R. and Mendez, Heather M. and Kubicek-Sutherland, Jessica Z. and Graves, Steven W. and Hengartner, Nicolas W. and Mukundan, Harshini and Bernardino de la Serna, ed., Jorge},
abstractNote = {Recognition of Pathogen-associated Molecular Patterns (PAMPs) by Toll-like receptors is central to innate immunity. Many bacterial PAMPs such as lipopolysaccharide (LPS) and lipoteichoic acid have amphiphilic properties. The hydrophobicity of amphiphilic PAMPs contributes to increasing entropy and causes these molecules to self-aggregate or bind host carrier proteins in aqueous physiological environments. The goal of this work was to determine how innate immune signaling is impacted by physical presentation and association of amphiphilic PAMPs with serum carrier proteins, using LPS as an example molecule. Specifically, we measured LPS-induced cytokine profiles in murine macrophages when the antigen was presented associated with the various serum carrier proteins in serum versus a serum-depleted system. Our study demonstrates that the observed cytokine profiles are dramatically different when LPS is presented in buffer, versus in serum when it is associated with proteins, specifically with respect to inhibition of pro-inflammatory cytokines in the latter. These studies suggest that LPS-mediated cytokine expression is dependent on its presentation in physiological systems. The amphiphilicity of bacterial PAMPs and consequent association with lipoproteins is a feature, which should be taken into account in the design of in vitro experiments. Further studies of the interdependencies of different serum carriers can identify pathways for drug delivery and diagnostics.},
doi = {10.1371/journal.pone.0198531},
journal = {PLoS ONE},
number = 6,
volume = 13,
place = {United States},
year = {2018},
month = {6}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1371/journal.pone.0198531

Citation Metrics:
Cited by: 1 work
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Effects of Ionic Strength on the Critical Micelle Concentration and the Surface Excess of Dodecyldimethylamine Oxide
journal, September 1997

  • Maeda, Hiroshi; Muroi, Shuichi; Kakehashi, Rie
  • The Journal of Physical Chemistry B, Vol. 101, Issue 38
  • DOI: 10.1021/jp9633815

Lysophosphatidic acid is a major serum noncytokine survival factor for murine macrophages which acts via the phosphatidylinositol 3-kinase signaling pathway.
journal, August 1998

  • Koh, J. S.; Lieberthal, W.; Heydrick, S.
  • Journal of Clinical Investigation, Vol. 102, Issue 4
  • DOI: 10.1172/JCI1002

LPS, TLR4 and infectious disease diversity
journal, January 2005

  • Miller, Samuel I.; Ernst, Robert K.; Bader, Martin W.
  • Nature Reviews Microbiology, Vol. 3, Issue 1
  • DOI: 10.1038/nrmicro1068

Lipoproteins attenuate TLR2 and TLR4 activation by bacteria and bacterial ligands with differences in affinity and kinetics
journal, October 2016

  • van Bergenhenegouwen, Jeroen; Kraneveld, Aletta D.; Rutten, Lieke
  • BMC Immunology, Vol. 17, Issue 1
  • DOI: 10.1186/s12865-016-0180-x

The role of membrane-bound LBP, endotoxin aggregates, and the MaxiK channel in LPS-induced cell activation
journal, June 2003


Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.
journal, September 1990

  • Harris, H. W.; Grunfeld, C.; Feingold, K. R.
  • Journal of Clinical Investigation, Vol. 86, Issue 3
  • DOI: 10.1172/JCI114765

Impedimetric biosensor based on self-assembled hybrid cystein-gold nanoparticles and CramoLL lectin for bacterial lipopolysaccharide recognition
journal, October 2011

  • Oliveira, Maria D. L.; Andrade, Cesar A. S.; Correia, Maria T. S.
  • Journal of Colloid and Interface Science, Vol. 362, Issue 1
  • DOI: 10.1016/j.jcis.2011.06.042

Endogenous ligands of Toll-like receptors
journal, June 2004

  • Tsan, Min-Fu; Gao, Baochong
  • Journal of Leukocyte Biology, Vol. 76, Issue 3
  • DOI: 10.1189/jlb.0304127

Lipoteichoic Acid and Toll-like Receptor 2 Internalization and Targeting to the Golgi Are Lipid Raft-dependent
journal, July 2004

  • Triantafilou, Martha; Manukyan, Maria; Mackie, Alan
  • Journal of Biological Chemistry, Vol. 279, Issue 39
  • DOI: 10.1074/jbc.M400466200

Induction of Toll-like receptor 4 in granulocytic and monocytic cells differentiated from HL-60 cells
journal, March 2001


Pattern Recognition Receptors and Inflammation
journal, March 2010


The role of lipoproteins and receptor-mediated endocytosis in the transport of bacterial lipopolysaccharide.
journal, April 1986

  • Van Lenten, B. J.; Fogelman, A. M.; Haberland, M. E.
  • Proceedings of the National Academy of Sciences, Vol. 83, Issue 8
  • DOI: 10.1073/pnas.83.8.2704

Colony-stimulating factors in inflammation and autoimmunity
journal, July 2008

  • Hamilton, John A.
  • Nature Reviews Immunology, Vol. 8, Issue 7
  • DOI: 10.1038/nri2356

Toll-like receptors in the induction of the innate immune response
journal, August 2000

  • Aderem, Alan; Ulevitch, Richard J.
  • Nature, Vol. 406, Issue 6797
  • DOI: 10.1038/35021228

LPS-binding proteins and receptors
journal, July 1998

  • Fenton, Matthew J.; Golenbock, Douglas T.
  • Journal of Leukocyte Biology, Vol. 64, Issue 1
  • DOI: 10.1002/jlb.64.1.25

Lipopolysaccharide Endotoxins
journal, June 2002


Pathogen Recognition and Innate Immunity
journal, February 2006


Triglyceride-rich lipoproteins improve survival when given after endotoxin in rats
journal, January 1995


TLRs and innate immunity
journal, February 2009


Biochemistry of Endotoxins
journal, June 1990


Bacterial Lipopolysaccharide Binds and Stimulates Cytokine-Producing Cells Before Neutralization by Endogenous Lipoproteins can Occur
journal, October 1998

  • Netea, Mihai G.; Demacker, Pierre N. M.; Kullberg, Bart Jan
  • Cytokine, Vol. 10, Issue 10
  • DOI: 10.1006/cyto.1998.0364

LPS induction of gene expression in human monocytes
journal, February 2001


Antibacterial Agents That Inhibit Lipid A Biosynthesis
journal, November 1996


MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4
journal, June 1999

  • Shimazu, Rintaro; Akashi, Sachiko; Ogata, Hirotaka
  • The Journal of Experimental Medicine, Vol. 189, Issue 11
  • DOI: 10.1084/jem.189.11.1777

TGF-β-activated kinase 1 mediates mechanical stress-induced IL-6 expression in osteoblasts
journal, May 2011

  • Fukuno, Naoto; Matsui, Hiroyuki; Kanda, Yoshiaki
  • Biochemical and Biophysical Research Communications, Vol. 408, Issue 2
  • DOI: 10.1016/j.bbrc.2011.02.127

Composition and structure of lipopolysaccharide-human plasma low density lipoprotein complex. Analytical ultracentrifugation,31P-NMR, ESR and fluorescence spectroscopy studies
journal, August 1989

  • Victorov, Alexander V.; Medvedeva, Natalia V.; Gladkaya, Elena M.
  • Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 984, Issue 1
  • DOI: 10.1016/0005-2736(89)90351-9

Pneumococcal Lipoteichoic Acid (LTA) Is Not as Potent as Staphylococcal LTA in Stimulating Toll-Like Receptor 2
journal, September 2003


Social stress increases the susceptibility to endotoxic shock
journal, April 2001


Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14
journal, January 1994


Conceptual and methodological issues relevant to cytokine and inflammatory marker measurements in clinical research
journal, January 2010

  • Zhou, Xin; Fragala, Maren S.; McElhaney, Janet E.
  • Current Opinion in Clinical Nutrition and Metabolic Care, Vol. 13, Issue 5
  • DOI: 10.1097/MCO.0b013e32833cf3bc

Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4
journal, October 2004


Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
journal, December 1998


Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids.
journal, January 1997

  • Yu, B.; Hailman, E.; Wright, S. D.
  • Journal of Clinical Investigation, Vol. 99, Issue 2
  • DOI: 10.1172/JCI119160

LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction
journal, January 2001

  • Vreugdenhil, Anita C. E.; Snoek, A. M. Patricia; van ‘t Veer, Cornelis
  • Journal of Clinical Investigation, Vol. 107, Issue 2
  • DOI: 10.1172/JCI10832

Membrane Insertion for the Detection of Lipopolysaccharides: Exploring the Dynamics of Amphiphile-in-Lipid Assays
journal, May 2016

  • Stromberg, Loreen R.; Hengartner, Nicolas W.; Swingle, Kirstie L.
  • PLOS ONE, Vol. 11, Issue 5, Article No. e0156295
  • DOI: 10.1371/journal.pone.0156295

The Susceptibility of mice to Bacterial Endotoxins
journal, March 1961


A Permanent Line of Macrophages with Normal Activity in a Primary Antibody Response In Vitro
journal, January 1973


Toll-Like Receptor 2 (TLR2)-Dependent-Positive and TLR2-Independent-Negative Regulation of Proinflammatory Cytokines by Mycobacterial Lipomannans
journal, March 2004

  • Quesniaux, Valerie J.; Nicolle, Delphine M.; Torres, David
  • The Journal of Immunology, Vol. 172, Issue 7
  • DOI: 10.4049/jimmunol.172.7.4425

Toll-like receptors: critical proteins linking innate and acquired immunity
journal, August 2001

  • Akira, Shizuo; Takeda, Kiyoshi; Kaisho, Tsuneyasu
  • Nature Immunology, Vol. 2, Issue 8
  • DOI: 10.1038/90609

Cytokine response by monocytes and macrophages to free and lipoprotein-bound lipopolysaccharide.
journal, January 1990


Caspase-1 processes IFN-γ-inducing factor and regulates LPS-induced IFN- γ production
journal, April 1997

  • Ghayur, Tariq; Banerjee, Subhashis; Hugunin, Margaret
  • Nature, Vol. 386, Issue 6625
  • DOI: 10.1038/386619a0

Unresponsiveness of MyD88-Deficient Mice to Endotoxin
journal, July 1999


The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
journal, April 2010

  • Kawai, Taro; Akira, Shizuo
  • Nature Immunology, Vol. 11, Issue 5
  • DOI: 10.1038/ni.1863

Critical Aggregation Concentrations of Gram-Negative Bacterial Lipopolysaccharides (LPS)
journal, December 1998

  • Aurell, Christina A.; Wistrom, Anders O.
  • Biochemical and Biophysical Research Communications, Vol. 253, Issue 1
  • DOI: 10.1006/bbrc.1998.9773

The role of HDL in innate immunity
journal, October 2010

  • Feingold, Kenneth R.; Grunfeld, Carl
  • Journal of Lipid Research, Vol. 52, Issue 1
  • DOI: 10.1194/jlr.E012138

Infection and Transformation of Mouse Peritoneal Macrophages by Simian Virus 40
journal, August 1971


Lipopolysaccharide Identification with Functionalized Polydiacetylene Liposome Sensors
journal, April 2004

  • Rangin, Marianne; Basu, Amit
  • Journal of the American Chemical Society, Vol. 126, Issue 16
  • DOI: 10.1021/ja039822x

Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides
journal, October 1976


Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses
journal, April 2009


Mycobacterial lipoarabinomannan mediates physical interactions between TLR1 and TLR2 to induce signaling
journal, August 2003


Detection and functional assessment of complement receptors on two murine macrophage-like cell lines
journal, September 1980


Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster
journal, June 2002


Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction
journal, April 1999

  • Chow, Jesse C.; Young, Donna W.; Golenbock, Douglas T.
  • Journal of Biological Chemistry, Vol. 274, Issue 16
  • DOI: 10.1074/jbc.274.16.10689

The role of lipid peroxidation and antioxidants in oxidative modification of LDL
journal, October 1992


LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria.
journal, May 1998

  • Lamping, N.; Dettmer, R.; Schröder, N. W.
  • Journal of Clinical Investigation, Vol. 101, Issue 10
  • DOI: 10.1172/JCI2338

Endogenous ligands of TLR2 and TLR4: agonists or assistants?
journal, February 2010


Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS
journal, September 1994


    Works referencing / citing this record:

    LPS-Binding Protein Modulates Acute Renal Fibrosis by Inducing Pericyte-to-Myofibroblast Trans-Differentiation through TLR-4 Signaling
    journal, July 2019

    • Castellano, Giuseppe; Stasi, Alessandra; Franzin, Rossana
    • International Journal of Molecular Sciences, Vol. 20, Issue 15
    • DOI: 10.3390/ijms20153682

    Understanding the Significance of Biochemistry in the Storage, Handling, Purification, and Sampling of Amphiphilic Mycolactone
    journal, April 2019