Dysregulated humoral immunity to nontyphoidal Salmonella in HIV-infected African adults.
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.
MacLennan
Calman A
CA
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
Gilchrist
James J
JJ
Gordon
Melita A
MA
Cunningham
Adam F
AF
Cobbold
Mark
M
Goodall
Margaret
M
Kingsley
Robert A
RA
van Oosterhout
Joep J G
JJ
Msefula
Chisomo L
CL
Mandala
Wilson L
WL
Leyton
Denisse L
DL
Marshall
Jennifer L
JL
Gondwe
Esther N
EN
Bobat
Saeeda
S
López-Macías
Constantino
C
Doffinger
Rainer
R
Henderson
Ian R
IR
Zijlstra
Eduard E
EE
Dougan
Gordon
G
Drayson
Mark T
MT
MacLennan
Ian C M
IC
Molyneux
Malcolm E
ME
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*
D000907:Antibodies, Bacterial; D019138:Antibodies, Blocking; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D019081:O Antigens