title: Subversion of innate and adaptive immune activation induced by structurally modified lipopolysaccharide from Salmonella typhimurium.
abstract: Salmonella are successful pathogens that infect millions of people every year. During infection, Salmonella typhimurium changes the structure of its lipopolysaccharide (LPS) in response to the host environment, rendering bacteria resistant to cationic peptide lysis in vitro. However, the role of these structural changes in LPS as in vivo virulence factors and their effects on immune responses and the generation of immunity are largely unknown. We report that modified LPS are less efficient than wild-type LPS at inducing pro-inflammatory responses. The impact of this LPS-mediated subversion of innate immune responses was demonstrated by increased mortality in mice infected with a non-lethal dose of an attenuated S. typhimurium strain mixed with the modified LPS moieties. Up-regulation of co-stimulatory molecules on antigen-presenting cells and CD4(+) T-cell activation were affected by these modified LPS. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing specific antibody responses. Immunization with modified LPS moiety preparations combined with experimental antigens, induced an impaired Toll-like receptor 4-mediated adjuvant effect. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing immunity against challenge with virulent S. typhimurium. Hence, changes in S. typhimurium LPS structure impact not only on innate immune responses but also on both humoral and cellular adaptive immune responses.
authors.affiliation: Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre 'Siglo XXI', Mexican Social Security Institute, Mexico City.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Pastelin-Palacios
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil-Cruz
authors.forename: Christian I
authors.initials: CI
authors.lastname: Pérez-Shibayama
authors.forename: Mario A
authors.initials: MA
authors.lastname: Moreno-Eutimio
authors.forename: Luisa
authors.initials: L
authors.lastname: Cervantes-Barragán
authors.forename: Lourdes
authors.initials: L
authors.lastname: Arriaga-Pizano
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: García-Zepeda
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Becker
authors.forename: Celia
authors.initials: C
authors.lastname: Alpuche-Aranda
authors.forename: Laura
authors.initials: L
authors.lastname: Bonifaz
authors.forename: John S
authors.initials: JS
authors.lastname: Gunn
authors.forename: Armando
authors.initials: A
authors.lastname: Isibasi
authors.forename: Constantino
authors.initials: C
authors.lastname: López-Macías
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D007113:Immunity, Innate / Q000276:immunology*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015394:Molecular Structure; D012486:Salmonella typhimurium / Q000737:chemistry / Q000276:immunology*; D015996:Survival Rate; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4