Dysregulated Humoral Immunity to Nontyphoidal Salmonella in HIV-Infected African Adults

• DOI: 10.1126/science.1180346
• Publication Date: 2010-04-22T18:59:11Z
• Authors: Calman A. MacLennan; James J. Gilchrist; Melita A. Gordon; Adam F. Cunningham; Mark Cobbold; Margaret Goodall; Robert A. Kingsley; Joep J. G. van Oo...; Chisomo L. Msefula; Wilson L. Mandala; Denisse L. Leyton; Jennifer L. Marshall; Esther N. Gondwe; Saeeda Bobat; Constantino López...; Rainer Doffinger; Ian R. Henderson; Eduard E. Zijlstra; Gordon Dougan; Mark T. Drayson; Ian C. M. MacLennan; Malcolm E. Molyneux
• Keywords: Adult; Lipopolysaccharides; Salmonella typhimurium; Malawi; bactericidal activity; Bacteremia; HIV Infections; antibody titer; Mice; antibody; Keywords: bacterium antibody; Animals; Humans; membrane protein; bacteremia; Antibodies, Blocking; Complement Activation; Multidisciplinary; human immunodeficiency virus; AIDS-Related Opportunistic Infections; adult; lipopolysaccharide; antibody specificity; article; O Antigens; bacterium; immunity; Antibodies, Bacterial; 3. Good health; cellular immuni; polysaccharide; 1000 General; Immunoglobulin G; Mutation; Salmonella Infections; Disease Susceptibility; protein; serum; Bacterial Outer Membrane Proteins

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.