title: Dysregulated humoral immunity to nontyphoidal Salmonella in HIV-infected African adults.
abstract: Nontyphoidal Salmonellae are a major cause of life-threatening bacteremia among HIV-infected individuals. Although cell-mediated immunity controls intracellular infection, antibodies protect against Salmonella bacteremia. We report that high-titer antibodies specific for Salmonella lipopolysaccharide (LPS) are associated with a lack of Salmonella-killing in HIV-infected African adults. Killing was restored by genetically shortening LPS from the target Salmonella or removing LPS-specific antibodies from serum. Complement-mediated killing of Salmonella by healthy serum is shown to be induced specifically by antibodies against outer membrane proteins. This killing is lost when excess antibody against Salmonella LPS is added. Thus, our study indicates that impaired immunity against nontyphoidal Salmonella bacteremia in HIV infection results from excess inhibitory antibodies against Salmonella LPS, whereas serum killing of Salmonella is induced by antibodies against outer membrane proteins.
authors.affiliation: Medical Research Council Centre for Immune Regulation and Clinical Immunology Service, Institute of Biomedical Research, School of Immunity and Infection, University of Birmingham, Birmingham, UK. c.maclennan@bham.ac.uk
authors.forename: Calman A
authors.initials: CA
authors.lastname: MacLennan
authors.forename: James J
authors.initials: JJ
authors.lastname: Gilchrist
authors.forename: Melita A
authors.initials: MA
authors.lastname: Gordon
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Mark
authors.initials: M
authors.lastname: Cobbold
authors.forename: Margaret
authors.initials: M
authors.lastname: Goodall
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kingsley
authors.forename: Joep J G
authors.initials: JJ
authors.lastname: van Oosterhout
authors.forename: Chisomo L
authors.initials: CL
authors.lastname: Msefula
authors.forename: Wilson L
authors.initials: WL
authors.lastname: Mandala
authors.forename: Denisse L
authors.initials: DL
authors.lastname: Leyton
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Marshall
authors.forename: Esther N
authors.initials: EN
authors.lastname: Gondwe
authors.forename: Saeeda
authors.initials: S
authors.lastname: Bobat
authors.forename: Constantino
authors.initials: C
authors.lastname: López-Macías
authors.forename: Rainer
authors.initials: R
authors.lastname: Doffinger
authors.forename: Ian R
authors.initials: IR
authors.lastname: Henderson
authors.forename: Eduard E
authors.initials: EE
authors.lastname: Zijlstra
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.forename: Ian C M
authors.initials: IC
authors.lastname: MacLennan
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D019138:Antibodies, Blocking / Q000097:blood / Q000276:immunology*; D016470:Bacteremia / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D003167:Complement Activation; D004198:Disease Susceptibility; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology*; D008295:Malawi; D051379:Mice; D009154:Mutation; D019081:O Antigens / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D019138:Antibodies, Blocking; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D019081:O Antigens