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

• Published in: The Journal of immunology (1950) 2018-10, Vol.201 (8), p.2377-2384
• Main Authors: Burgess, Edward J, Hoyt, Laura R, Randall, Matthew J, Mank, Madeleine M, Bivona, 3rd, Joseph J, Eisenhauer, Philip L, Botten, Jason W, Ballif, Bryan A, Lam, Ying-Wai, Wargo, Matthew J, Boyson, Jonathan E, Ather, Jennifer L, Poynter, Matthew E
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1800503

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 , 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 -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.