S considered to be the predominant source of infection, even though transmission through non-livestock sources including water and milk are increasingly implicated (1?). The clinical spectrum of C. jejuni infection can variety from asymptomatic carriage to acute inflammatory diarrhea to autoimmune complications. The presence of leukocytes in stools during the very first couple of days of infection is indicative of an early innate inflammatory response that aids bacterial clearance when contributing to clinical illness within the susceptible (4). Preceding studies have highlighted the prospective role of Tolllike receptors (TLRs)3 in mediating early host immunity to C. jejuni (five, six). The bacterium evades recognition by human TLR5 resulting from amino acid sequence alterations inside the flagellin protein; this phenomenon has also been noted in other -proteobacteria like Helicobacter pylori, suggesting that negation of TLR5-mediated antimicrobial immunity may give strategic advantage to particular enteropathogens (7). The glycolipid lipooligosaccharide/lipopolysaccharide (LOS/LPS) moieties of C. jejuni and H. pylori, respectively, show divergent responses upon TLR4 activation.4-Acetoxy-2-naphthoic acid structure The tetraacylated H. pylori LPS exhibits low reactivity; in comparison, the hexaacylated C. jejuni LOS is usually a potent TLR4 agonist (5, six, 8 ?0). The latter observation raises the hypothesis that C.1781098-86-9 Chemscene jejuni LOS/TLR4 activation might contribute for the acute mucosal inflammation generally seen in human infections. The association of C. jejuni strains with LOS modifications that market proinflammatory responses with improved severity of enteritis supports this hypothesis (9, 11). The structure of both the lipid A (LA) along with the oligosaccharide (OS) components of your LOS/LPS moiety can significantly* This perform was supported in aspect by a Charlotte and Yule Bogue researchfellowship from University College London (to H. N. S.), the Biomedical Analysis Council, UK, and Investigation Service of the Usa Division of Veterans Affairs Merit Critique Award BX000727 (to G. A. J.). 1 Present address: Dept. of Cellular Microbiology, Max Planck Inst. for Infection Biology, Charite Platz, Berlin 10117, Germany. ?2 To whom correspondence need to be addressed: Dept. 111W1, Veterans Affairs Health-related Center, 4150 Clement St., San Francisco, CA 94121. E-mail: [email protected]. The abbreviations used are: TLR, Toll-like receptor; LOS, lipooligosaccharide; OS, oligosaccharide; LA, lipid A; SA, sialic acid; GBS, Guillain-Barre syn?drome; GlcN, 2-amino-2-deoxy-D-glucose; GlcN3N, two,3-diamino-2,3-dideoxy-D-glucose; PEA, phosphoethanolamine; DPLA, diphosphorylated LA; Kdo, 3-deoxy-D-manno-oct-2-ulosonic acid; Hep, heptose; Hex, hexose; HexNAc, N-acetylhexosamine; OAc, O-acetate; PPEA, phosphoryl-PEA; Neu5Ac, N-acetylneuraminic acid; TRIF, Toll/IL-1 receptor (TIR) domaincontaining adaptor inducing IFN- .PMID:33503225 JULY 5, 2013 ?VOLUME 288 ?NUMBERJOURNAL OF BIOLOGICAL CHEMISTRYC. jejuni LOS-TLR4 Interactionsalter TLR4 activation and subsequent responses (12). The heterogeneous nature of C. jejuni LOS LA and OS structures has been noted previously (13?6). To date, 19 unique genetic loci for the OS genes happen to be identified in C. jejuni strains (16). Five of those LOS classes encode sialic acid (SA) biosynthesis genes that involve neuB1 (SA synthase), cstII (SA transferase), and neuA1 (CMP-Neu5Ac synthase). OS sialylation is related with the neuropathy Guillain-Barre syndrome (GBS) ?and with elevated TLR4 function and severity of gastroent.