Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Abstract

Bacteremia caused by nontyphoidal strains ofSalmonellais endemic among African children. Case-fatality rates are high and antibiotic resistance increasing, but no vaccine is currently available. T cells are important for clearance ofSalmonellainfection within macrophages, but in Africa, invasiveSalmonelladisease usually manifests in the blood and affects children between 4 months and 2 y of age, when anti-Salmonellaantibody is absent. We have previously found a role for complement-fixing bactericidal antibody in protecting these children. Here we show that opsonic activity of antibody and complement is required for oxidative burst and killing ofSalmonellaby blood cells in Africans. Induction of neutrophil oxidative burst correlated with anti-SalmonellaIgG and IgM titers and C3 deposition on bacteria and was significantly lower in African children younger than 2 y compared with older children. PreopsonizingSalmonellawith immune serum overcame this deficit, indicating a requirement for antibody and/or complement. Using different opsonization procedures, both antibody and complement were found to be necessary for optimal oxidative burst, phagocytosis and killing of nontyphoidalSalmonellaby peripheral blood cells in Africans. Although most strains of African nontyphoidalSalmonellacan be killed with antibody and complement alone, phagocytes in the presence of specific antibody and complement can kill strains resistant to killing by immune serum. These findings increase the likelihood that an antibody-inducing vaccine will protect against invasive nontyphoidalSalmonelladisease in African children.