title: Treponemal phospholipids inhibit innate immune responses induced by pathogen-associated molecular patterns.
abstract: Host innate immune responses to microbial components, known as pathogen-associated molecular patterns (PAMPs), are regulated and modified by cellular receptors and serum proteins, including Toll-like receptors (TLRs), CD14, and LPS-binding protein (LBP). We demonstrated that a treponemal membrane lipid inhibited PAMPs-induced immune responses. The chemical structure of the lipid was elucidated as a phosphatidylglycerol (PG) derivative, which is scarce in most mammalian tissues, but relatively abundant in treponemal membrane lipids. Natural and synthetic PG counterparts as well as related natural anionic phospholipids, phosphatidylinositol, phosphatidylserine, and cardiolipin, also demonstrated an inhibitory effect. Further, we noted that PG inhibited PAMPs-induced immune responses by blocking the binding of PAMPs with LBP and CD14. In addition, PG decreased proinflammatory cytokine production in serum of LPS-injected mice and depressed abscess formation in mice infected with treponemes. These results suggest that treponemal phospholipid interfere the function of LBP/CD14 and act as a modulator of innate immune responses.
authors.affiliation: Department of Oral Microbiology, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Asai
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ogawa
mesh_terms: D000038:Abscess / Q000382:microbiology; D000209:Acute-Phase Proteins; D000818:Animals; D015153:Blotting, Western; D002308:Cardiolipins / Q000494:pharmacology; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D007109:Immunity / Q000187:drug effects*; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D008562:Membrane Glycoproteins; D008563:Membrane Lipids / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000502:physiology; D010715:Phosphatidylglycerols / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014208:Treponema / Q000737:chemistry*; D014211:Treponemal Infections / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002308:Cardiolipins; D002352:Carrier Proteins; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008156:Luciferases; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D016328:NF-kappa B; D010715:Phosphatidylglycerols; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D010743:Phospholipids; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol