Dysregulated humoral immunity to nontyphoidal Salmonella in HIV-Infected african adults

Calman A. MacLennan, James J. Gilchrist, Melita A. Gordon, Adam F. Cunningham, Mark Cobbold, Margaret Goodall, Robert A. Kingsley, Joep J.G. Van Oosterhout, Chisomo L. Msefula, Wilson L. Mandala, Denisse L. Leyton, Jennifer L. Marshall, Esther N. Gondwe, Saeeda Bobat, Constantino López-Macias, Rainer Doffinger, Ian R. Henderson, Eduard E. Zijlstra, Gordon Dougan, Mark T. DraysonIan C.M. MacLennan, Malcolm E. Molyneux

Research output: Contribution to journalArticlepeer-review

135 Citations (Scopus)


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 Solmonella-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 languageEnglish
Pages (from-to)508-512
Number of pages5
Issue number5977
Publication statusPublished - 23 Apr 2010
Externally publishedYes


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