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

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:
 [1] ;  [1] ; ORCiD logo [2] ;  [3] ;  [2] ; ORCiD logo [1]
  1. Univ. of New Mexico, Albuquerque, NM (United States). Center for Biomedical Engineering; Los Alamos National Lab. (LANL), Los Alamos, NM (United States); The New Mexico Consortium, Los Alamos, NM (United States)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  3. Univ. of New Mexico, Albuquerque, NM (United States). Center for Biomedical Engineering
Publication Date:
Report Number(s):
LA-UR-17-27524
Journal ID: ISSN 1932-6203
Grant/Contract Number:
AC52-06NA25396; 2012-68003-30155
Type:
Published Article
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 13; Journal Issue: 6; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
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)
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
OSTI Identifier:
1454322
Alternate Identifier(s):
OSTI ID: 1475350

Stromberg, Loreen R., Mendez, Heather M., Kubicek-Sutherland, Jessica Z., Graves, Steven W., Hengartner, Nicolas W., and Mukundan, Harshini. Presentation matters: Impact of association of amphiphilic LPS with serum carrier proteins on innate immune signaling. United States: N. p., Web. doi:10.1371/journal.pone.0198531.
Stromberg, Loreen R., Mendez, Heather M., Kubicek-Sutherland, Jessica Z., Graves, Steven W., Hengartner, Nicolas W., & Mukundan, Harshini. Presentation matters: Impact of association of amphiphilic LPS with serum carrier proteins on innate immune signaling. United States. doi:10.1371/journal.pone.0198531.
Stromberg, Loreen R., Mendez, Heather M., Kubicek-Sutherland, Jessica Z., Graves, Steven W., Hengartner, Nicolas W., and Mukundan, Harshini. 2018. "Presentation matters: Impact of association of amphiphilic LPS with serum carrier proteins on innate immune signaling". United States. doi: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},
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}
}

Works referenced in this record:

Pathogen Recognition and Innate Immunity
journal, February 2006

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