The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children
Calman A. MacLennan, … , Malcolm E. Molyneux, Mark T. Drayson
Calman A. MacLennan, … , Malcolm E. Molyneux, Mark T. Drayson
Published March 20, 2008
Citation Information: J Clin Invest. 2008;118(4):1553-1562. https://doi.org/10.1172/JCI33998.
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Research Article Immunology

The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children

Abstract

Nontyphoidal strains of Salmonella (NTS) are a common cause of bacteremia among African children. Cell-mediated immune responses control intracellular infection, but they do not protect against extracellular growth of NTS in the blood. We investigated whether antibody protects against NTS bacteremia in Malawian children, because we found this condition mainly occurs before 2 years of age, with relative sparing of infants younger than 4 months old. Sera from all healthy Malawian children tested aged more than 16 months contained anti-Salmonella antibody and successfully killed NTS. Killing was mediated by complement membrane attack complex and not augmented in the presence of blood leukocytes. Sera from most healthy children less than 16 months old lacked NTS-specific antibody, and sera lacking antibody did not kill NTS despite normal complement function. Addition of Salmonella-specific antibody, but not mannose-binding lectin, enabled NTS killing. All NTS strains tested had long-chain lipopolysaccharide and the rck gene, features that resist direct complement-mediated killing. Disruption of lipopolysaccharide biosynthesis enabled killing of NTS by serum lacking Salmonella-specific antibody. We conclude that Salmonella-specific antibody that overcomes the complement resistance of NTS develops by 2 years of life in Malawian children. This finding and the age-incidence of NTS bacteremia suggest that antibody protects against NTS bacteremia and support the development of vaccines against NTS that induce protective antibody.

Authors

Calman A. MacLennan, Esther N. Gondwe, Chisomo L. Msefula, Robert A. Kingsley, Nicholas R. Thomson, Sarah A. White, Margaret Goodall, Derek J. Pickard, Stephen M. Graham, Gordon Dougan, C. Anthony Hart, Malcolm E. Molyneux, Mark T. Drayson

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Figure 5

Killing of NTS by serum from Malawian children compared with anti-Salmonella IgG and IgM titers and complement C3 and membrane attack complex deposition in vitro killing of S. Typhimurium isolate D23580 by serum at 180 minutes.

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The rck gene of invasive NTS isolates from Malawi. (A) P...
(A and B) NTS killing compared with specific anti-Salmonella D23580 IgG (A) and IgM (B) levels. (C and D) NTS killing compared with complement C3 (C) and C5b-9 membrane attack complex (MAC; D) deposition on D23580. The initial concentration was 106 salmonellae/ml. Each point corresponds to serum from 1 child, either less than (filled circle) or more than (open circle) 16 months of age. Numbers at top right denote the number of points in the indicated quadrants, as divided by threshold for normal killing (more or less than 1.5 U Ig, 100 U C3, and 0.6 U C5b-9 membrane attack complex) and normal or impaired killing (more or less, respectively, than 1.2 log10 kill).