title: Activation of toll-like receptor 2 (TLR2) and TLR4/MD2 by Neisseria is independent of capsule and lipooligosaccharide (LOS) sialylation but varies widely among LOS from different strains.
abstract: Lipooligosaccharide (LOS) structure and capsular polysaccharide of Neisseria meningitidis each greatly influence the virulence of the organism and the quality of host innate immune responses. In this study, we found that production of the proinflammatory cytokine tumor necrosis factor (TNF) by a human monocyte-derived cell line (THP-1) exposed to strains of N. meningitidis lacking capsule and/or with truncated LOS was similar to that elicited by the isogenic wild-type strain. These mutants also exhibited no difference in induction of the interleukin-8 (IL-8) promoter in a transfected HeLa cell system of Toll-like receptor 2 (TLR2) and TLR4/MD2 signaling. However, purified LOS from diverse strains of Neisseria (both N. meningitidis and N. gonorrhoeae) caused widely variant levels of IL-8 promoter induction in cells expressing MD2 that correlated with the production of TNF from THP-1 cells. These data suggest that although modification of the oligosaccharide chain of LOS and/or absence of capsule do not affect cell signaling mediated by TLR4/MD2, fine-structural differences in the LOS do influence signaling through TLR4/MD2 and, through this pathway, influence some of the proinflammatory responses elicited by Neisseria.
authors.affiliation: Division of Genomic Medicine, Royal Hallamshire Hospital, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: Alison C
authors.initials: AC
authors.lastname: Pridmore
authors.forename: Gary A
authors.initials: GA
authors.lastname: Jarvis
authors.forename: Constance M
authors.initials: CM
authors.lastname: John
authors.forename: Dominic L
authors.initials: DL
authors.lastname: Jack
authors.forename: Steven K
authors.initials: SK
authors.lastname: Dower
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
mesh_terms: D016667:Bacterial Capsules / Q000502:physiology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D013045:Species Specificity; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C023023:lipid-linked oligosaccharides; D019158:N-Acetylneuraminic Acid