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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.

Original publication

DOI

10.1126/science.1180346

Type

Journal article

Journal

Science

Publication Date

23/04/2010

Volume

328

Pages

508 - 512

Keywords

AIDS-Related Opportunistic Infections, Adult, Animals, Antibodies, Bacterial, Antibodies, Blocking, Bacteremia, Bacterial Outer Membrane Proteins, Complement Activation, Disease Susceptibility, HIV Infections, Humans, Immunoglobulin G, Lipopolysaccharides, Malawi, Mice, Mutation, O Antigens, Salmonella Infections, Salmonella typhimurium