Bacterial Lipoproteins Constitute the TLR2-Stimulating Activity of Serum Amyloid A

J Immunol. 2018 Oct 15;201(8):2377-2384. doi: 10.4049/jimmunol.1800503. Epub 2018 Aug 29.


Studies comparing endogenous and recombinant serum amyloid A (SAA) have generated conflicting data on the proinflammatory function of these proteins. In exploring this discrepancy, we found that in contrast to commercially sourced recombinant human SAA1 (hSAA1) proteins produced in Escherichia coli, hSAA1 produced from eukaryotic cells did not promote proinflammatory cytokine production from human or mouse cells, induce Th17 differentiation, or stimulate TLR2. Proteomic analysis of E. coli-derived hSAA1 revealed the presence of numerous bacterial proteins, with several being reported or probable lipoproteins. Treatment of hSAA1 with lipoprotein lipase or addition of a lipopeptide to eukaryotic cell-derived hSAA1 inhibited or induced the production of TNF-α from macrophages, respectively. Our results suggest that a function of SAA is in the binding of TLR2-stimulating bacterial proteins, including lipoproteins, and demand that future studies of SAA employ a recombinant protein derived from eukaryotic cells.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Animals
  • Cell Differentiation
  • Cytokines / metabolism
  • Escherichia coli / genetics
  • Escherichia coli Proteins / immunology
  • HEK293 Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Leukocytes, Mononuclear / immunology*
  • Lipoproteins / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Proteins / genetics
  • Serum Amyloid A Protein / genetics
  • Serum Amyloid A Protein / immunology*
  • Th17 Cells / immunology*
  • Toll-Like Receptor 2 / agonists*


  • Cytokines
  • Escherichia coli Proteins
  • Inflammation Mediators
  • Lipoproteins
  • Recombinant Proteins
  • Serum Amyloid A Protein
  • TLR2 protein, human
  • Toll-Like Receptor 2