Dysregulated Humoral Immunity to Nontyphoidal Salmonella in HIV-Infected African Adults
MacLennan CA., Gilchrist JJ., Gordon MA., Cunningham AF., Cobbold M., Goodall M., Kingsley RA., van Oosterhout JJG., Msefula CL., Mandala WL., Leyton DL., Marshall JL., Gondwe EN., Bobat S., López-Macías C., Doffinger R., Henderson IR., Zijlstra EE., Dougan G., Drayson MT., MacLennan ICM., Molyneux ME.
HIV and Salmonella HIV-positive individuals who are infected with nontyphoidal strains of Salmonella enterica often succumb to high morbidity and mortality. Why this is the case is unknown. MacLennan et al. (p. 508 ; see the Perspective by Moir and Fauci ) have uncovered a dysregulated antibody response to Salmonella that is the likely culprit. Sera from HIV-infected individuals do a poor job of killing S. Typhimurium, despite surprisingly elevated antibody titers. Experiments showed that HIV-infected serum inhibited the power of normal serum to kill Salmonella . Inhibition was specific to antibodies against lipopolysaccharide (LPS), a component of the cell wall of Salmonella . Hence, HIV-infected sera was able to kill Salmonella strains lacking LPS, and removing LPS immunoglobulin G from infected sera permitted Salmonella killing. Thus, not only does HIV cause defects in cell-mediated immunity but it also seems to impair humoral immunity, with severe consequences for multiple infections.